Phosphate in Physiological and Pathological Mineralization: Important yet Often Unheeded

Wen Qin , San-yang Yu , Jia-lu Gao , Jian-fei Yan , Qian-qian Wan , Shuai-lin Jia , Franklin Tay , Kai Jiao , Lina Niu

MedComm ›› 2025, Vol. 6 ›› Issue (7) : e70298

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MedComm ›› 2025, Vol. 6 ›› Issue (7) : e70298 DOI: 10.1002/mco2.70298
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Phosphate in Physiological and Pathological Mineralization: Important yet Often Unheeded

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Abstract

Phosphate is an important element in biological processes, particularly in the formation and metabolism of mineralized tissues such as bones and teeth. The imbalance of phosphate is also closely related with pathological mineralization. Restoring the phosphate homeostasis is an attractive target to treat diseases related with pathological mineralization. However, the inherent consistency of phosphate's role in both physiological and pathological mineralization has been overlooked in previous investigations. This review highlights the multifaceted role of phosphate as a building block, and as a signaling molecule that regulates the activity of mineralizing cells in both physiological and pathological mineralization. This direct and indirect role of phosphate acts as a bridge between physiological and pathological mineralization. The review also discusses the genetic mutations associated with phosphate-related mineralization disorders, emphasizing the need for further genetic and molecular research to uncover additional factors and mechanisms. Future research directions proposed include enhancing our understanding of phosphate sensing and regulation mechanisms, investigating new therapeutic agents, and developing reliable biomarkers for early diagnosis and treatment of phosphate-related mineralization disorders. By advancing our knowledge in these areas, we can improve the prevention, diagnosis, and treatment of phosphate-related mineralization disorders to enhance patient outcomes and their quality of life.

Keywords

pathological mineralization / phosphate homeostasis / phosphate metabolism disorders / physiological mineralization / therapeutic strategies

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Wen Qin, San-yang Yu, Jia-lu Gao, Jian-fei Yan, Qian-qian Wan, Shuai-lin Jia, Franklin Tay, Kai Jiao, Lina Niu. Phosphate in Physiological and Pathological Mineralization: Important yet Often Unheeded. MedComm, 2025, 6(7): e70298 DOI:10.1002/mco2.70298

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References

[1]

I. M. Shapiro, M. V. Risbud, W. J. Landis, “Toward Understanding the Cellular Control of Vertebrate Mineralization: The Potential Role of Mitochondria,” Bone 185 (2024): 117112.

[2]

M. Murshed, “Mechanism of Bone Mineralization,” Cold Spring Harbor Perspectives in Medicine 10 (2020): a040667.

[3]

W. Qin, C. Wang, Y. Ma, et al., “Microbe-Mediated Extracellular and Intracellular Mineralization: Environmental, Industrial, and Biotechnological Applications,” Advanced Materials 34 (2022): e2109924.

[4]

P. A. Cohen, J. V. Strauss, A. D. Rooney, M. Sharma, and N. Tosca, “Controlled Hydroxyapatite Biomineralization in an ∼810 Million-Year-Old Unicellular Eukaryote,” Science Advances 3 (2017): e1700095.

[5]

Y. Dauphin, “A Brief History of Biomineralization Studies,” ACS Biomaterials Science & Engineering 9 (2023): 1774-1790.

[6]

D. J. E. Murdock, “The ‘Biomineralization Toolkit’ and the Origin of Animal Skeletons,” Biological Reviews of the Cambridge Philosophical Society 95 (2020): 1372-1392.

[7]

M. S. Clark, “Molecular Mechanisms of Biomineralization in Marine Invertebrates,” Journal of Experimental Biology 223, no. pt 11 (2020): jeb206961.

[8]

T. Kono, T. Sakae, H. Nakada, T. Kaneda, and H. Okada, “Confusion Between Carbonate Apatite and Biological Apatite (Carbonated Hydroxyapatite) in Bone and Teeth,” Minerals 12 (2022): 170.

[9]

Z. Fang, Z. Yan, S. Li, et al., “Localization of Calmodulin and Calmodulin-Like Protein and Their Functions in Biomineralization in P. fucata,” Progress in Natural Science 18 (2008): 405-412.

[10]

M. Eckstein, M. Vaeth, C. Fornai, et al., “Store-Operated Ca2+ Entry Controls Ameloblast Cell Function and Enamel Development,” JCI Insight 2 (2017): e91166.

[11]

S. K. Bhadada, S. D. Rao, “Role of Phosphate in Biomineralization,” Calcified Tissue International 108 (2021): 32-40.

[12]

B. Hoac, T. Kiffer-Moreira, J. L. Millán, and M. D. McKee, “Polyphosphates Inhibit Extracellular Matrix Mineralization in MC3T3-E1 Osteoblast Cultures,” Bone 53 (2013): 478-486.

[13]

M. C Yadav, A. M. S. Simão, S. Narisawa, et al., “Loss of Skeletal Mineralization by the Simultaneous Ablation of PHOSPHO1 and Alkaline Phosphatase Function: A Unified Model of the Mechanisms of Initiation of Skeletal Calcification,” Journal of Bone and Mineral Research 26 (2011): 286-297.

[14]

K. Wang, F. Luo, L. Wang, et al., “Biomineralization From the Perspective of Ion Aggregation: Calcium Phosphate Nucleation in the Physiological Environment,” ACS Applied Materials & Interfaces 13 (2021): 49519-49534.

[15]

P. H. Schlesinger, D. T. Braddock, Q. C. Larrouture, et al., “Phylogeny and Chemistry of Biological Mineral Transport,” Bone 141 (2020): 115621.

[16]

W. N. Addison, F. Azari, E. S. Sørensen, M. T. Kaartinen, and M. D. McKee, “Pyrophosphate Inhibits Mineralization of Osteoblast Cultures by Binding to Mineral, Up-Regulating Osteopontin, and Inhibiting Alkaline Phosphatase Activity,” Journal of Biological Chemistry 282 (2007): 15872-15883.

[17]

A. Arnold, E. Dennison, C. S. Kovacs, et al., “Hormonal Regulation of Biomineralization,” Nature Reviews Endocrinology 17 (2021): 261-275.

[18]

C. A. Wagner, “The Basics of Phosphate Metabolism,” Nephrology, Dialysis, Transplantation 39 (2024): 190-201.

[19]

B. L. Foster, K. A. Tompkins, R. B. Rutherford, et al., “Phosphate: Known and Potential Roles During Development and Regeneration of Teeth and Supporting Structures,” Birth Defects Research Part C, Embryo Today 84 (2008): 281-314.

[20]

F. Della-Felice, A. de Andrade Bartolomeu, R. A. Pilli, “The Phosphate Ester Group in Secondary Metabolites,” Natural Product Reports 39 (2022): 1066-1107.

[21]

V. Mavridou, M. S. King, S. Tavoulari, J. J. Ruprecht, S. M. Palmer, E. R. S. Kunji, “Substrate Binding in the Mitochondrial ADP/ATP Carrier Is a Step-Wise Process Guiding the Structural Changes in the Transport Cycle,” Nature Communications 13 (2022): 3585.

[22]

W. E. G. Müller, S. Wang, M. Neufurth, et al., “Polyphosphate as a Donor of High-Energy Phosphate for the Synthesis of ADP and ATP,” Journal of Cell Science 130 (2017): 2747-2756.

[23]

J. A. McCubrey, W. S. May, V. Duronio, and A. Mufson, “Serine/Threonine Phosphorylation in Cytokine Signal Transduction,” Leukemia 14 (2000): 9-21.

[24]

T. Hunter, “A Journey From Phosphotyrosine to Phosphohistidine and Beyond,” Molecular Cell 82 (2022): 2190-2200.

[25]

M. Rigoulet, C. Bouchez, P. Paumard, et al., “Cell Energy Metabolism: An Update,” Biochimica et Biophysica (BBA) - Bioenergetics 1861 (2020): 148276.

[26]

F. B. Rudolph, “The Biochemistry and Physiology of Nucleotides,” Journal of Nutrition 124 (1994): 124S-127S.

[27]

A. E. Engelhart, N. V. Hud, “Primitive Genetic Polymers,” Cold Spring Harbor Perspectives in Biology 2 (2010): a002196.

[28]

J. D. Salcedo-Betancourt, O. W. Moe, “The Effects of Acid on Calcium and Phosphate Metabolism,” International Journal of Molecular Sciences 25 (2024): 2081.

[29]

S. C. Kamerlin, P. K. Sharma, R. B. Prasad, and A. Warshel, “Why Nature Really Chose Phosphate,” Quarterly Reviews of Biophysics 46 (2013): 1-132.

[30]

T. Hunter, “Why Nature Chose Phosphate to Modify Proteins,” Philosophical Transactions of the Royal Society of London. Series B: Biological Sciences 367 (2012): 2513-2516.

[31]

J. E. Vance, “Phospholipid Synthesis and Transport in Mammalian Cells,” Traffic (Copenhagen, Denmark) 16 (2015): 1-18.

[32]

N. Hernando, K. Gagnon, E. Lederer, “Phosphate Transport in Epithelial and Nonepithelial Tissue,” Physiological Reviews 101 (2021): 1-35.

[33]

L. Figueres, S. Beck-Cormier, L. Beck, and J. Marks, “The Complexities of Organ Crosstalk in Phosphate Homeostasis: Time to Put Phosphate Sensing Back in the Limelight,” International Journal of Molecular Sciences 22 (2021): 5701.

[34]

C. Zechner, E. P. Rhee, “Phosphate Sensing in Health and Disease,” Current Opinion in Nephrology and Hypertension 33 (2024): 361-367.

[35]

N. Bon, G. Couasnay, A. Bourgine, et al., “Phosphate (Pi)-regulated Heterodimerization of the High-Affinity Sodium-Dependent Pi Transporters PiT1/Slc20a1 and PiT2/Slc20a2 Underlies Extracellular Pi Sensing Independently of Pi Uptake,” Journal of Biological Chemistry 293 (2018): 2102-2114.

[36]

N. Bon, G. Frangi, S. Sourice, J. Guicheux, S. Beck-Cormier, L. Beck, “Phosphate-Dependent FGF23 Secretion Is Modulated by PiT2/Slc20a2,” Molecular Metabolism 11 (2018): 197-204.

[37]

Y. Takashi, “Phosphate-Sensing Mechanisms and Functions of Phosphate as a First Messenger,” Endocrine Journal 71 (2024): 335-343.

[38]

Y. Takashi, S. Fukumoto, “Phosphate-Sensing and Regulatory Mechanism of FGF23 Production,” Journal of Endocrinological Investigation 43 (2020): 877-883.

[39]

C. H. Lin, C. H. Su, P. P. Hwang, “Calcium-Sensing Receptor Mediates Ca(2+) Homeostasis by Modulating Expression of PTH and Stanniocalcin,” Endocrinology 155 (2014): 56-67.

[40]

P. P. Centeno, A. Herberger, H. Mun, et al., “Phosphate Acts Directly on the Calcium-Sensing Receptor to Stimulate Parathyroid Hormone Secretion,” Nature Communications 10 (2019): 4693.

[41]

M. Bonora, S. Patergnani, A. Rimessi, et al., “ATP Synthesis and Storage,” Purinergic Signal 8 (2012): 343-357.

[42]

M. Bohdanowicz, S. Grinstein, “Role of Phospholipids in Endocytosis, Phagocytosis, and Macropinocytosis,” Physiological Reviews 93 (2013): 69-106.

[43]

R. Wild, R. Gerasimaite, J. Jung, et al., “Control of Eukaryotic Phosphate Homeostasis by Inositol Polyphosphate Sensor Domains,” Science 352 (2016): 986-990.

[44]

X. Li, C. Gu, S. Hostachy, et al., “Control of XPR1-Dependent Cellular Phosphate Efflux by InsP8 Is an Exemplar for Functionally-Exclusive Inositol Pyrophosphate Signaling,” Proceedings National Academy of Science USA 117 (2020): 3568-3574.

[45]

M. S. Wilson, H. J. Jessen, A. Saiardi, “The Inositol Hexakisphosphate Kinases IP6K1 and -2 Regulate Human Cellular Phosphate Homeostasis, Including XPR1-Mediated Phosphate Export,” Journal of Biological Chemistry 294 (2019): 11597-11608.

[46]

T. Knöpfel, N. Himmerkus, D. Günzel, M. Bleich, N. Hernando, C. A. Wagner, “Paracellular Transport of Phosphate Along the Intestine,” American Journal of Physiology-Gastrointestinal and Liver Physiology 317 (2019): G233-241.

[47]

J. Yee, D. Rosenbaum, J. W. Jacobs, and S. M. Sprague, “Small Intestinal Phosphate Absorption: Novel Therapeutic Implications,” American Journal of Nephrology 52 (2021): 522-530.

[48]

E. A. B. Hughes, T. E. Robinson, D. B. Bassett, S. C. Cox, L. M. Grover, “Critical and Diverse Roles of Phosphates in Human Bone Formation,” Journal of Materials Chemistry B 7 (2019): 7460-7470.

[49]

H. Komaba, M. Fukagawa, “Phosphate - A Poison for Humans?,” Kidney International 90 (2016): 753-763.

[50]

J. Biber, H. Murer, N. Mohebbi, and C. A. Wagner, “Renal Handling of Phosphate and Sulfate,” Comprehensive Physiology 4 (2014): 771-792.

[51]

Y. Sabbagh, S. P. O'Brien, W. Song, et al., “Intestinal npt2b Plays a Major Role in Phosphate Absorption and Homeostasis,” Journal of the American Society of Nephrology 20 (2009): 2348-2358.

[52]

Y. Ichida, S. Ohtomo, T. Yamamoto, et al., “Evidence of an Intestinal Phosphate Transporter Alternative to Type IIb Sodium-Dependent Phosphate Transporter in Rats With Chronic Kidney Disease,” Nephrology, Dialysis, Transplantation 36 (2021): 68-75.

[53]

E. M. Pastor-Arroyo, T. Knöpfel, P. H. Imenez Silva, et al., “Intestinal Epithelial Ablation of Pit-2/Slc20a2 in Mice Leads to Sustained Elevation of Vitamin D3 Upon Dietary Restriction of Phosphate,” Acta Physiologica 230 (2020): e13526.

[54]

S. Shenolikar, J. W. Voltz, C. M. Minkoff, J. B. Wade, and E. J. Weinman, “Targeted Disruption of the Mouse NHERF-1 Gene Promotes Internalization of Proximal Tubule Sodium-Phosphate Cotransporter Type IIa and Renal Phosphate Wasting,” Proceedings National Academy of Science USA 99 (2002): 11470-11475.

[55]

N. Déliot, N. Hernando, Z. Horst-Liu, et al., “Parathyroid Hormone Treatment Induces Dissociation of Type IIa Na+-P(i) Cotransporter-Na+/H+ Exchanger Regulatory Factor-1 Complexes,” American Journal of Physiology Cell Physiology 289 (2005): C159-C167.

[56]

E. J. Weinman, D. Steplock, S. Shenolikar, and R. Biswas, “Fibroblast Growth Factor-23-Mediated Inhibition of Renal Phosphate Transport in Mice Requires Sodium-Hydrogen Exchanger Regulatory Factor-1 (NHERF-1) and Synergizes With Parathyroid Hormone,” Journal of Biological Chemistry 286 (2011): 37216-37221.

[57]

M. A. Lacerda-Abreu, J. R. Meyer-Fernandes, “Extracellular Inorganic Phosphate-Induced Release of Reactive Oxygen Species: Roles in Physiological Processes and Disease Development,” International Journal of Molecular Sciences 22 (2021): 7768.

[58]

H. C. Blair, Q. C. Larrouture, Y. Li, et al., “Osteoblast Differentiation and Bone Matrix Formation In Vivo and In Vitro,” Tissue Engineering Part B Reviews 23 (2017): 268-280.

[59]

M. Kerschnitzki, A. Akiva, A. Ben Shoham, et al., “Bone Mineralization Pathways During the Rapid Growth of Embryonic Chicken Long Bones,” Journal of Structural Biology 195 (2016): 82-92.

[60]

I. M. Shapiro, M. V. Risbud, W. J. Landis, “Toward Understanding the Cellular Control of Vertebrate Mineralization: The Potential Role of Mitochondria,” Bone 185 (2024): 117112.

[61]

S. G. Wolf, Y. Mutsafi, T. Dadosh, et al., “3D Visualization of Mitochondrial Solid-Phase Calcium Stores in Whole Cells,” Elife 6 (2017): e29929.

[62]

Y. Zhang, S. Ma, J. Nie, et al., “Journey of Mineral Precursors in Bone Mineralization: Evolution and Inspiration for Biomimetic Design,” Small 20 (2024): e2207951.

[63]

D. Pei, J. Sun, C. Zhu, et al., “Contribution of Mitophagy to Cell-Mediated Mineralization: Revisiting a 50-Year-Old Conundrum,” Advancement of Science 5 (2018): 1800873.

[64]

T. Michigami, M. Kawai, M. Yamazaki, and K. Ozono, “Phosphate as a Signaling Molecule and Its Sensing Mechanism,” Physiological Reviews 98 (2018): 2317-2348.

[65]

S. Fukumoto, “The Role of Bone in Phosphate Metabolism,” Molecular and Cellular Endocrinology 310 (2009): 63-70.

[66]

M. S. Razzaque, “Bone-Kidney Axis in Systemic Phosphate Turnover,” Archives of Biochemistry and Biophysics 561 (2014): 154-158.

[67]

T. Michigami, “Roles of Osteocytes in Phosphate Metabolism,” Frontiers in Endocrinology 13 (2022): 967774.

[68]

J. Gattineni, P. Alphonse, Q. Zhang, N. Mathews, C. M. Bates, M. Baum, “Regulation of Renal Phosphate Transport by FGF23 Is Mediated by FGFR1 and FGFR4,” American Journal of Physiology Renal Physiology 306 (2014): F351-358.

[69]

J. Gattineni, C. Bates, K. Twombley, et al., “FGF23 Decreases Renal NaPi-2a and NaPi-2c Expression and Induces Hypophosphatemia In Vivo Predominantly via FGF Receptor 1,” American Journal of Physiology Renal Physiology 297 (2009): F282-F291.

[70]

R. Agoro, K. E. White, “Regulation of FGF23 Production and Phosphate Metabolism by Bone-Kidney Interactions,” Nature Reviews Nephrology 19 (2023): 185-193.

[71]

A. S. Dusso, M. Rodriguez, “Enhanced Induction of Cyp24a1 by FGF23 but Low Serum 24,25-Dihydroxyvitamin D in CKD: Implications for Therapy,” Kidney International 82 (2012): 1046-1049.

[72]

I. Z. Ben-Dov, H. Galitzer, V. Lavi-Moshayoff, et al., “The Parathyroid Is a Target Organ for FGF23 in Rats,” Journal of Clinical Investigation 117 (2007): 4003-4008.

[73]

D. Bacic, M. LeHir, J. Biber, B. Kaissling, H. Murer, C. Wagner, “The Renal Na+/Phosphate Cotransporter NaPi-IIa Is Internalized via the Receptor-Mediated Endocytic Route in Response to Parathyroid Hormone,” Kidney International 69 (2006): 495-503.

[74]

T. Fujii, H. Segawa, A. Hanazaki, et al., “Role of the Putative PKC Phosphorylation Sites of the Type IIc Sodium-Dependent Phosphate Transporter in Parathyroid Hormone Regulation,” Clinical and Experimental Nephrology 23 (2019): 898-907.

[75]

M. J. Horwitz, M. B. Tedesco, S. M. Sereika, et al., “Continuous PTH and PTHrP Infusion Causes Suppression of Bone Formation and Discordant Effects on 1,25(OH)2 Vitamin D,” Journal of Bone and Mineral Research 20 (2005): 1792-1803.

[76]

S. Yoon, M. B. Meyer, C. Arevalo, et al., “A Parathyroid Hormone/Salt-Inducible Kinase Signaling Axis Controls Renal Vitamin D Activation and Organismal Calcium Homeostasis,” Journal of Clinical Investigation 133 (2023): e163627.

[77]

K. Katai, K. Miyamoto, S. Kishida, et al., “Regulation of Intestinal Na+-Dependent Phosphate Co-Transporters by a Low-Phosphate Diet and 1,25-Dihydroxyvitamin D3,” Biochemical Journal 343 (1999): 705-712.

[78]

R. Rizzoli, H. Fleisch, J. P. Bonjour, “Role of 1,25-Dihydroxyvitamin D3 on Intestinal Phosphate Absorption in Rats With a Normal Vitamin D Supply,” Journal of Clinical Investigation 60 (1977): 639-647.

[79]

T. K. Barthel, D. R. Mathern, G. K. Whitfield, et al., “1,25-Dihydroxyvitamin D3/VDR-Mediated Induction of FGF23 as Well as Transcriptional Control of Other Bone Anabolic and Catabolic Genes That Orchestrate the Regulation of Phosphate and Calcium Mineral Metabolism,” Journal of Steroid Biochemistry and Molecular Biology 103 (2007): 381-388.

[80]

H. Xie, I. Bastepe, W. Zhou, et al., “1,25-Dihydroxyvitamin D3 Regulates Furin-Mediated FGF23 Cleavage,” JCI Insight 8 (2023): e168957.

[81]

O. I. Kolek, E. R. Hines, M. D. Jones, et al., “1Alpha,25-Dihydroxyvitamin D3 Upregulates FGF23 Gene Expression in Bone: The Final Link in a Renal-Gastrointestinal-Skeletal Axis That Controls Phosphate Transport,” American Journal of Physiology-Gastrointestinal and Liver Physiology 289 (2005): G1036-G1042.

[82]

D. R. Martin, C. S. Ritter, E. Slatopolsky, and A. J. Brown, “Acute Regulation of Parathyroid Hormone by Dietary Phosphate,” American Journal of Physiology. Endocrinology and Metabolism 289 (2005): E729-E734.

[83]

A. Daryadel, B. Haykir, C. J. Küng, et al., “Acute Adaptation of Renal Phosphate Transporters in the Murine Kidney to Oral Phosphate Intake Requires Multiple Signals,” Acta Physiologica 235 (2022): e13815.

[84]

T. Iwayama, P. Bhongsatiern, M. Takedachi, and S. Murakami, “Matrix Vesicle-Mediated Mineralization and Potential Applications,” Journal of Dental Research 101 (2022): 1554-1562.

[85]

K. Rilla, A. Mustonen, U. T. Arasu, K. Härkönen, J. Matilainen, P. Nieminen, “Extracellular Vesicles Are Integral and Functional Components of the Extracellular Matrix,” Matrix Biology 75-76 (2019): 201-219.

[86]

H. G. Sebinelli, L. H. S. Andrilli, B. Z. Favarin, et al., “Shedding Light on the Role of Na,K-ATPase as a Phosphatase During Matrix-Vesicle-Mediated Mineralization,” International Journal of Molecular Sciences 23 (2022): 15072.

[87]

J. Szymański, J. Janikiewicz, B. Michalska, et al., “Interaction of Mitochondria With the Endoplasmic Reticulum and Plasma Membrane in Calcium Homeostasis, Lipid Trafficking and Mitochondrial Structure,” International Journal of Molecular Sciences 18 (2017): 1576.

[88]

R. Filadi, P. Theurey, P. Pizzo, “The Endoplasmic Reticulum-Mitochondria Coupling in Health and Disease: Molecules, Functions and Significance,” Cell Calcium 62 (2017): 1-15.

[89]

C. Tang, Y. Wei, L. Gu, et al., “Biomineral Precursor Formation Is Initiated by Transporting Calcium and Phosphorus Clusters From the Endoplasmic Reticulum to Mitochondria,” Advancement of Science 7 (2020): 1902536.

[90]

J. Lombard, P. López-García, D. Moreira, “The Early Evolution of Lipid Membranes and the Three Domains of Life,” Nature Reviews Microbiology 10 (2012): 507-515.

[91]

S. Roberts, S. Narisawa, D. Harmey, J. L. Millán, and C. Farquharson, “Functional Involvement of PHOSPHO1 in Matrix Vesicle-Mediated Skeletal Mineralization,” Journal of Bone and Mineral Research 22 (2007): 617-627.

[92]

B. Favarin, M. Bolean, A. Ramos, et al., “Lipid Composition Modulates ATP Hydrolysis and Calcium Phosphate Mineral Propagation by TNAP-Harboring Proteoliposomes,” Archives of Biochemistry and Biophysics 691 (2020): 108482.

[93]

M. C. Yadav, M. Bottini, E. Cory, et al., “Skeletal Mineralization Deficits and Impaired Biogenesis and Function of Chondrocyte-Derived Matrix Vesicles in Phospho1(-/-) and Phospho1/Pit1 Double-Knockout Mice,” Journal of Bone and Mineral Research 31 (2016): 1275-1286.

[94]

S. J. Roberts, A. J. Stewart, P. J. Sadler, and C. Farquharson, “Human PHOSPHO1 Exhibits High Specific Phosphoethanolamine and Phosphocholine Phosphatase Activities,” Biochemical Journal 382 (2004): 59-65.

[95]

A. J. Stewart, D. T. K. Leong, C. Farquharson, “PLA2 and ENPP6 May Act in Concert to Generate Phosphocholine From the Matrix Vesicle Membrane During Skeletal Mineralization,” FASEB Journal 32 (2018): 20-25.

[96]

K. Kato, H. Nishimasu, D. Oikawa, et al., “Structural Insights Into cGAMP Degradation by Ecto-Nucleotide Pyrophosphatase Phosphodiesterase 1,” Nature Communications 9 (2018): 4424.

[97]

K. Kato, H. Nishimasu, S. Okudaira, et al., “Crystal Structure of Enpp1, an Extracellular Glycoprotein Involved in Bone Mineralization and Insulin Signaling,” Proceedings National Academy of Science USA 109 (2012): 16876-16881.

[98]

L. H. S. Andrilli, H. G. Sebinelli, B. Z. Favarin, et al., “NPP1 and TNAP Hydrolyze ATP Synergistically During Biomineralization,” Purinergic Signalling 19 (2023): 353-366.

[99]

T. Michigami, K. Ozono, “Roles of Phosphate in Skeleton,” Frontiers in Endocrinology 10 (2019): 180.

[100]

I. R. Orriss, T. R. Arnett, R. G. Russell, “Pyrophosphate: A Key Inhibitor of Mineralisation,” Current Opinion in Pharmacology 28 (2016): 57-68.

[101]

Y. Liang, Z. Hu, Q. Li, and X. Liu, “Pyrophosphate Inhibits Periodontal Ligament Stem Cell Differentiation and Mineralization Through MAPK Signaling Pathways,” Journal of Periodontal Research 56 (2021): 982-990.

[102]

X. Zhou, Y. Cui, X. Zhou, and J. Han, “Phosphate/Pyrophosphate and MV-Related Proteins in Mineralisation: Discoveries From Mouse Models,” International Journal of Biological Sciences 8 (2012): 778-790.

[103]

R. Garimella, X. Bi, H. C. Anderson, and N. P. Camacho, “Nature of Phosphate Substrate as a Major Determinant of Mineral Type Formed in Matrix Vesicle-Mediated In Vitro Mineralization: An FTIR Imaging Study,” Bone 38 (2006): 811-817.

[104]

T. Yamamoto, T. Hasegawa, T. Mae, et al., “Comparative Immunolocalization of Tissue Nonspecific Alkaline Phosphatase and Ectonucleotide Pyrophosphatase/Phosphodiesterase 1 in Murine Bone,” Journal of Oral Biosciences 63 (2021): 259-264.

[105]

M. Gao, Q. Su, T. Liang, et al., “Transcriptional Activation of ENPP1 by Osterix in Osteoblasts and Osteocytes,” European Cells & Materials [Electronic Resource] 36 (2018): 1-14.

[106]

T. Hasegawa, H. Hongo, T. Yamamoto, et al., “Matrix Vesicle-Mediated Mineralization and Osteocytic Regulation of Bone Mineralization,” International Journal of Molecular Sciences 23 (2022): 9941.

[107]

S. Boonrungsiman, E. Gentleman, R. Carzaniga, et al., “The Role of Intracellular Calcium Phosphate in Osteoblast-Mediated Bone Apatite Formation,” Proceedings National Academy of Science USA 109 (2012): 14170-14175.

[108]

T. Iwayama, T. Okada, T. Ueda, et al., “Osteoblastic Lysosome Plays a Central Role in Mineralization,” Science Advances 5 (2019): eaax0672.

[109]

J. Mahamid, A. Sharir, D. Gur, E. Zelzer, L. Addadi, S. Weiner, “Bone Mineralization Proceeds Through Intracellular Calcium Phosphate Loaded Vesicles: A Cryo-Electron Microscopy Study,” Journal of Structural Biology 174 (2011): 527-535.

[110]

M. A. Cruz, C. R. Ferreira, C. B. Tovani, et al., “Phosphatidylserine Controls Calcium Phosphate Nucleation and Growth on Lipid Monolayers: A Physicochemical Understanding of Matrix Vesicle-Driven Biomineralization,” Journal of Structural Biology 212 (2020): 107607.

[111]

J. S. Plaut, A. Strzelecka-Kiliszek, L. Bozycki, et al., “Quantitative Atomic Force Microscopy Provides New Insight Into Matrix Vesicle Mineralization,” Archives of Biochemistry and Biophysics 667 (2019): 14-21.

[112]

L. Cui, D. A. Houston, C. Farquharson, and V. E. MacRae, “Characterisation of Matrix Vesicles in Skeletal and Soft Tissue Mineralisation,” Bone 87 (2016): 147-158.

[113]

J. Thomas, H. Worch, B. Kruppke, and T. Gemming, “Contribution to Understand the Biomineralization of Bones,” Journal of Bone and Mineral Metabolism 38 (2020): 456-468.

[114]

Y. Ma, S. E. Hoff, X. Huang, et al., “Involvement of Prenucleation Clusters in Calcium Phosphate Mineralization of Collagen,” Acta Biomaterialia 120 (2021): 213-223.

[115]

S. Shan, Z. Tang, K. Sun, et al., “ACP-Mediated Phase Transformation for Collagen Mineralization: A New Understanding of the Mechanism,” Advanced Healthcare Materials 13 (2024): e2302418.

[116]

C. Guibert, J. Landoulsi, “Enzymatic Approach in Calcium Phosphate Biomineralization: A Contribution to Reconcile the Physicochemical With the Physiological View,” International Journal of Molecular Sciences 22 (2021): 12957.

[117]

A. A. Zalutskaya, M. K. Cox, M. B. Demay, “Phosphate Regulates Embryonic Endochondral Bone Development,” Journal of Cellular Biochemistry 108 (2009): 668-674.

[118]

R. Alexander, N. Debiec, M. S. Razzaque, and P. He, “Inorganic Phosphate-Induced Cytotoxicity,” IUBMB Life 74 (2022): 117-124.

[119]

F. C. Ko, M. M. Kobelski, W. Zhang, G. M. Grenga, J. S. Martins, M. B. Demay, “Phosphate Restriction Impairs mTORC1 Signaling Leading to Increased Bone Marrow Adipose Tissue and Decreased Bone in Growing Mice,” Journal of Bone and Mineral Research 36 (2021): 1510-1520.

[120]

X. Wang, H. C. Schroder, B. Diehl-Seifert, et al., “Dual Effect of Inorganic Polymeric Phosphate/Polyphosphate on Osteoblasts and Osteoclasts In Vitro,” Journal of Tissue Engineering and Regenerative Medicine 7 (2013): 767-776.

[121]

W. N. Addison, M. D. McKee, “Inositol Hexakisphosphate Inhibits Mineralization of MC3T3-E1 Osteoblast Cultures,” Bone 46 (2010): 1100-1107.

[122]

S. Chande, C. Bergwitz, “Role of Phosphate Sensing in Bone and Mineral Metabolism,” Nature Reviews Endocrinology 14 (2018): 637-655.

[123]

M. Julien, D. Magne, M. Masson, et al., “Phosphate Stimulates Matrix Gla Protein Expression in Chondrocytes Through the Extracellular Signal Regulated Kinase Signaling Pathway,” Endocrinology 148 (2007): 530-537.

[124]

D. Magne, G. Bluteau, C. Faucheux, et al., “Phosphate Is a Specific Signal for ATDC5 Chondrocyte Maturation and Apoptosis-Associated Mineralization: Possible Implication of Apoptosis in the Regulation of Endochondral Ossification,” Journal of Bone and Mineral Research 18 (2003): 1430-1442.

[125]

M. Kimata, T. Michigami, K. Tachikawa, et al., “Signaling of Extracellular Inorganic Phosphate Up-Regulates Cyclin D1 Expression in Proliferating Chondrocytes via the Na+/Pi Cotransporter Pit-1 and Raf/MEK/ERK Pathway,” Bone 47 (2010): 938-947.

[126]

H. J. Kim, J. D. Delaney, T. Kirsch, “The Role of Pyrophosphate/Phosphate Homeostasis in Terminal Differentiation and Apoptosis of Growth Plate Chondrocytes,” Bone 47 (2010): 657-665.

[127]

T. Orfanidou, K. N. Malizos, S. Varitimidis, A. Tsezou, “1,25-Dihydroxyvitamin D(3) and Extracellular Inorganic Phosphate Activate Mitogen-Activated Protein Kinase Pathway Through Fibroblast Growth Factor 23 Contributing to Hypertrophy and Mineralization in Osteoarthritic Chondrocytes,” Experimental Biology and Medicine 237 (2012): 241-253.

[128]

P. S. Yadav, G. Papaioannou, M. M. Kobelski, and M. B. Demay, “Phosphate-Induced Activation of VEGFR2 Leads to Caspase-9-Mediated Apoptosis of Hypertrophic Chondrocytes,” Iscience 26 (2023): 107548.

[129]

F. Cailotto, S. Sebillaud, P. Netter, J. Y. Jouzeau, and A. Bianchi, “The Inorganic Pyrophosphate Transporter ANK Preserves the Differentiated Phenotype of Articular Chondrocyte,” Journal of Biological Chemistry 285 (2010): 10572-10582.

[130]

G. R. J. Beck, “Inorganic Phosphate as a Signaling Molecule in Osteoblast Differentiation,” Journal of Cellular Biochemistry 90 (2003): 234-243.

[131]

J. R. Farley, S. L. Hall, M. A. Tanner, and J. E. Wergedal, “Specific Activity of Skeletal Alkaline Phosphatase in Human Osteoblast-Line Cells Regulated by Phosphate, Phosphate Esters, and Phosphate Analogs and Release of Alkaline Phosphatase Activity Inversely Regulated by Calcium,” Journal of Bone and Mineral Research 9 (1994): 497-508.

[132]

R. Zhang, Y. Lu, L. Ye, et al., “Unique Roles of Phosphorus in Endochondral Bone Formation and Osteocyte Maturation,” Journal of Bone and Mineral Research 26 (2011): 1047-1056.

[133]

K. A. Conrads, M. Yi, K. A. Simpson, et al., “A Combined Proteome and Microarray Investigation of Inorganic Phosphate-Induced Pre-Osteoblast Cells,” Molecular & Cellular Proteomics 4 (2005): 1284-1296.

[134]

Y. Yoshiko, G. A. Candeliere, N. Maeda, and J. E. Aubin, “Osteoblast Autonomous Pi Regulation via Pit1 Plays a Role in Bone Mineralization,” Molecular and Cellular Biology 27 (2007): 4465-4474.

[135]

S. Khoshniat, A. Bourgine, M. Julien, et al., “Phosphate-Dependent Stimulation of MGP and OPN Expression in Osteoblasts via the ERK1/2 Pathway Is Modulated by Calcium,” Bone 48 (2011): 894-902.

[136]

J. Nishino, M. Yamazaki, M. Kawai, et al., “Extracellular Phosphate Induces the Expression of Dentin Matrix Protein 1 Through the FGF Receptor in Osteoblasts,” Journal of Cellular Biochemistry 118 (2017): 1151-1163.

[137]

G. Beck, “Inorganic Phosphate Regulates Multiple Genes During Osteoblast Differentiation, Including Nrf2,” Experimental Cell Research 288 (2003): 288-300.

[138]

G. R. J. Beck, B. Zerler, E. Moran, “Phosphate Is a Specific Signal for Induction of Osteopontin Gene Expression,” Proceedings National Academy of Science USA 97 (2000): 8352-8357.

[139]

S. C. Chaudhary, M. Kuzynski, M. Bottini, et al., “Phosphate Induces Formation of Matrix Vesicles During Odontoblast-Initiated Mineralization In Vitro,” Matrix Biology 52-54 (2016): 284-300.

[140]

M. A. Lacerda-Abreu, T. Russo-Abrahão, D. Cosentino-Gomes, et al., “H+-Dependent Inorganic Phosphate Transporter in Breast Cancer Cells: Possible Functions in the Tumor Microenvironment,” Biochimica et Biophysica Acta - Molecular Basis of Disease 1865 (2019): 2180-2188.

[141]

A. Elson, A. Anuj, M. Barnea-Zohar, and N. Reuven, “The Origins and Formation of Bone-Resorbing Osteoclasts,” Bone 164 (2022): 116538.

[142]

S. M. Abdelmagid, A. Zajac, I. Salhab, and H. D. Nah, “Inorganic Pyrophosphate Promotes Osteoclastogenic Commitment and Survival of Bone Marrow Derived Monocytes Mediated by Egr-1 Up-Regulation and MITF Phosphorylation,” BioRxiv (2020): 2020-10.

[143]

M. Arioka, F. Takahashi-Yanaga, N. Tatsumoto, and T. Sasaguri, “Inorganic Phosphate-Induced Impairment of Osteoclast Cell-Cell Fusion by the Inhibition of AP-1-Mediated DC-STAMP Expression,” Biochemical and Biophysical Research Communications 493 (2017): 9-13.

[144]

E. M'Baya-Moutoula, L. Louvet, V. Metzinger-Le Meuth, Z. A. Massy, and L. Metzinger, “High Inorganic Phosphate Concentration Inhibits Osteoclastogenesis by Modulating miR-223,” Biochimica et Biophysica Acta 1852 (2015): 2202-2212.

[145]

T. Hayashibara, T. Hiraga, A. Sugita, et al., “Regulation of Osteoclast Differentiation and Function by Phosphate: Potential Role of Osteoclasts in the Skeletal Abnormalities in Hypophosphatemic Conditions,” Journal of Bone and Mineral Research 22 (2007): 1743-1751.

[146]

A. Mozar, N. Haren, M. Chasseraud, et al., “High Extracellular Inorganic Phosphate Concentration Inhibits RANK-RANKL Signaling in Osteoclast-Like Cells,” Journal of Cellular Physiology 215 (2008): 47-54.

[147]

M. Kanatani, T. Sugimoto, J. Kano, M. Kanzawa, and K. Chihara, “Effect of High Phosphate Concentration on Osteoclast Differentiation as Well as Bone-Resorbing Activity,” Journal of Cellular Physiology 196 (2003): 180-189.

[148]

A. George, A. Veis, “Phosphorylated Proteins and Control Over Apatite Nucleation, Crystal Growth, and Inhibition,” Chemical Reviews 108 (2008): 4670-4693.

[149]

A. S. Deshpande, P. Fang, X. Zhang, T. Jayaraman, C. Sfeir, E. Beniash, “Primary Structure and Phosphorylation of Dentin Matrix Protein 1 (DMP1) and Dentin Phosphophoryn (DPP) Uniquely Determine Their Role in Biomineralization,” Biomacromolecules 12 (2011): 2933-2945.

[150]

G. K. Hunter, “Role of Osteopontin in Modulation of Hydroxyapatite Formation,” Calcified Tissue International 93 (2013): 348-354.

[151]

A. Gericke, C. Qin, L. Spevak, et al., “Importance of Phosphorylation for Osteopontin Regulation of Biomineralization,” Calcified Tissue International 77 (2005): 45-54.

[152]

N. Shin, H. Yamazaki, E. Beniash, et al., “Amelogenin Phosphorylation Regulates Tooth Enamel Formation by Stabilizing a Transient Amorphous Mineral Precursor,” Journal of Biological Chemistry 295 (2020): 1943-1959.

[153]

N. Abbarin, S. San Miguel, J. Holcroft, K. Iwasaki, and B. Ganss, “The Enamel Protein Amelotin Is a Promoter of Hydroxyapatite Mineralization,” Journal of Bone and Mineral Research 30 (2015): 775-785.

[154]

R. Villa-Bellosta, “Vascular Calcification: A Passive Process That Requires Active Inhibition,” Biology 13 (2024): 111.

[155]

R. Nicoll, M. Y. Henein, “The Predictive Value of Arterial and Valvular Calcification for Mortality and Cardiovascular Events,” International Journal of Cardiology Heart & Vessels 3 (2014): 1-5.

[156]

C. M. Giachelli, “Vascular Calcification Mechanisms,” Journal of the American Society of Nephrology 15 (2004): 2959-2964.

[157]

J. A. Leopold, “Vascular Calcification: An Age-Old Problem of Old Age,” Circulation 127 (2013): 2380-2382.

[158]

N. R. Sutton, R. Malhotra, C. St Hilaire, et al., “Molecular Mechanisms of Vascular Health: Insights From Vascular Aging and Calcification,” Arteriosclerosis, Thrombosis, and Vascular Biology 43 (2023): 15-29.

[159]

L. A. Pescatore, L. F. Gamarra, M. Liberman, “Multifaceted Mechanisms of Vascular Calcification in Aging,” Arteriosclerosis, Thrombosis, and Vascular Biology 39 (2019): 1307-1316.

[160]

C. M. Shanahan, “Mechanisms of Vascular Calcification in CKD-Evidence for Premature Ageing?,” Nature Reviews Nephrology 9 (2013): 661-670.

[161]

J. K. Snell-Bergeon, M. J. Budoff, J. E. Hokanson, “Vascular Calcification in Diabetes: Mechanisms and Implications,” Current Diabetes Reports 13 (2013): 391-402.

[162]

S. Ghosh, D. Luo, W. He, J. Chen, X. Su, H. Huang, “Diabetes and Calcification: The Potential Role of Anti-Diabetic Drugs on Vascular Calcification Regression,” Pharmacological Research 158 (2020): 104861.

[163]

G. Lefthériotis, L. Omarjee, O. L. Saux, et al., “The Vascular Phenotype in Pseudoxanthoma Elasticum and Related Disorders: Contribution of a Genetic Disease to the Understanding of Vascular Calcification,” Frontiers in Genetics 4 (2013): 4.

[164]

D. P. Germain, “Pseudoxanthoma Elasticum,” Orphanet Journal of Rare Diseases 12 (2017): 85.

[165]

A. M. Boyce, R. I. Gafni, C. R. Ferreira, “Generalized Arterial Calcification of Infancy: New Insights, Controversies, and Approach to Management,” Current Osteoporosis Report 18 (2020): 232-241.

[166]

C. Wider, D. W. Dickson, K. J. Schweitzer, D. F. Broderick, Z. K. Wszolek, “Familial Idiopathic Basal Ganglia Calcification: A Challenging Clinical-Pathological Correlation,” Journal of Neurology 256 (2009): 839-842.

[167]

G. Lee, C. Yeh, J. Wu, et al., “TLR2 Promotes Vascular Smooth Muscle Cell Chondrogenic Differentiation and Consequent Calcification via the Concerted Actions of Osteoprotegerin Suppression and IL-6-Mediated RANKL Induction,” Arteriosclerosis, Thrombosis, and Vascular Biology 39 (2019): 432-445.

[168]

J. Voelkl, T. T. Luong, R. Tuffaha, et al., “SGK1 Induces Vascular Smooth Muscle Cell Calcification Through NF-κB Signaling,” Journal of Clinical Investigation 128 (2018): 3024-3040.

[169]

A. L. Negri, “Role of Prolyl Hydroxylase/HIF-1 Signaling in Vascular Calcification,” Clinical Kidney Journal 16 (2022): 205-209.

[170]

R. Villa-Bellosta, M. R. Hamczyk, V. Andrés, “Alternatively Activated Macrophages Exhibit an Anticalcifying Activity Dependent on Extracellular ATP/Pyrophosphate Metabolism,” American Journal of Physiology Cell Physiology 310 (2016): C788-C799.

[171]

M. Cozzolino, P. Ciceri, A. Galassi, et al., “The Key Role of Phosphate on Vascular Calcification,” Toxins 11 (2019): 213.

[172]

C. M. Shanahan, M. H. Crouthamel, A. Kapustin, and C. M. Giachelli, “Arterial Calcification in Chronic Kidney Disease: Key Roles for Calcium and Phosphate,” Circulation Research 109 (2011): 697-711.

[173]

J. Voelkl, F. Lang, K. U. Eckardt, et al., “Signaling Pathways Involved in Vascular Smooth Muscle Cell Calcification During Hyperphosphatemia,” Cellular and Molecular Life Sciences 76 (2019): 2077-2091.

[174]

R. Villa-Bellosta, J. Egido, “Phosphate, Pyrophosphate, and Vascular Calcification: A Question of Balance,” European Heart Journal 38 (2017): 1801-1804.

[175]

A. Nagy, D. Pethő, R. Gesztelyi, et al., “BGP-15 Inhibits Hyperglycemia-Aggravated VSMC Calcification Induced by High Phosphate,” International Journal of Molecular Sciences 22 (2021): 9263.

[176]

N. Ding, Y. Lv, H. Su, et al., “Vascular Calcification in CKD: New Insights Into Its Mechanisms,” Journal of Cellular Physiology 238 (2023): 1160-1182.

[177]

R. Buchet, C. Tribes, V. Rouaix, et al., “Hydrolysis of Extracellular ATP by Vascular Smooth Muscle Cells Transdifferentiated Into Chondrocytes Generates Pi but Not PPi,” International Journal of Molecular Sciences 22 (2021): 2948.

[178]

S. G. Holt, E. R. Smith, “Fetuin-A-Containing Calciprotein Particles in Mineral Trafficking and Vascular Disease,” Nephrology Dialysis Transplantation 31 (2016): 1583-1587.

[179]

R. Villa-Bellosta, “New Insights Into Endogenous Mechanisms of Protection Against Arterial Calcification,” Atherosclerosis 306 (2020): 68-74.

[180]

R. A. Albright, P. Stabach, W. Cao, et al., “ENPP1-Fc Prevents Mortality and Vascular Calcifications in Rodent Model of Generalized Arterial Calcification of Infancy,” Nature Communications 6 (2015): 10006.

[181]

V. Pomozi, C. B. Julian, J. Zoll, et al., “Dietary Pyrophosphate Modulates Calcification in a Mouse Model of Pseudoxanthoma Elasticum: Implication for Treatment of Patients,” Journal of Investigative Dermatology 139 (2019): 1082-1088.

[182]

D. Dedinszki, F. Szeri, E. Kozák, et al., “Oral Administration of Pyrophosphate Inhibits Connective Tissue Calcification,” EMBO Molecular Medicine 9 (2017): 1463-1470.

[183]

M. Fakhry, M. Roszkowska, A. Briolay, et al., “TNAP Stimulates Vascular Smooth Muscle Cell Trans-Differentiation Into Chondrocytes Through Calcium Deposition and BMP-2 Activation: Possible Implication in Atherosclerotic Plaque Stability,” Biochimica et Biophysica Acta - Molecular Basis of Disease 1863 (2017): 643-653.

[184]

A. Y. Savinov, M. Salehi, M. C. Yadav, I. Radichev, J. L. Millán, O. V. Savinova, “Transgenic Overexpression of Tissue-Nonspecific Alkaline Phosphatase (TNAP) in Vascular Endothelium Results in Generalized Arterial Calcification,” Journal of the American Heart Association 4 (2015): e002499.

[185]

B. Chen, Y. Zhao, D. Han, et al., “Wnt1 Inhibits Vascular Smooth Muscle Cell Calcification by Promoting ANKH Expression,” Journal of Molecular and Cellular Cardiology 135 (2019): 10-21.

[186]

J. Huang, A. E. Snook, J. Uitto, and Q. Li, “Adenovirus-Mediated ABCC6 Gene Therapy for Heritable Ectopic Mineralization Disorders,” Journal of Investigative Dermatology 139 (2019): 1254-1263.

[187]

Q. Li, J. Huang, A. B. Pinkerton, et al., “Inhibition of Tissue-Nonspecific Alkaline Phosphatase Attenuates Ectopic Mineralization in the Abcc6-/- Mouse Model of PXE but Not in the Enpp1 Mutant Mouse Models of GACI,” Journal of Investigative Dermatology 139 (2019): 360-368.

[188]

S. Zununi Vahed, S. Mostafavi, S. M. Hosseiniyan Khatibi, M. M. Shoja, and M. Ardalan, “Vascular Calcification: An Important Understanding in Nephrology,” Vascular Health and Risk Management 16 (2020): 167-180.

[189]

G. Leftheriotis, N. Navasiolava, L. Clotaire, et al., “Relationships Between Plasma Pyrophosphate, Vascular Calcification and Clinical Severity in Patients Affected by Pseudoxanthoma Elasticum,” Journal of Clinical Medicine 11 (2022): 2588.

[190]

J. Zhao, J. Kingman, J. P. Sundberg, J. Uitto, and Q. Li, “Plasma PPi Deficiency Is the Major, but Not the Exclusive, Cause of Ectopic Mineralization in an Abcc6-/- Mouse Model of PXE,” Journal of Investigative Dermatology 137 (2017): 2336-2343.

[191]

Z. Cheng, K. O'Brien, J. Howe, et al., “INZ-701 Prevents Ectopic Tissue Calcification and Restores Bone Architecture and Growth in ENPP1-Deficient Mice,” Journal of Bone and Mineral Research 36 (2021): 1594-1604.

[192]

D. Ralph, M. Levine, J. L. Millán, J. Uitto, and Q. Li, “Weighing the Evidence for the Roles of Plasma versus Local Pyrophosphate in Ectopic Calcification Disorders,” Journal of Bone and Mineral Research 38 (2023): 457-463.

[193]

W. J. Moorhead, C. C. Chu, R. A. Cuevas, et al., “Dysregulation of FOXO1 (Forkhead Box O1 Protein) Drives Calcification in Arterial Calcification Due to Deficiency of CD73 and Is Present in Peripheral Artery Disease,” Arteriosclerosis, Thrombosis, and Vascular Biology 40 (2020): 1680-1694.

[194]

I. Hozumi, H. Kurita, K. Ozawa, et al., “Inorganic Phosphorus (Pi) in CSF Is a Biomarker for SLC20A2-Associated Idiopathic Basal Ganglia Calcification (IBGC1),” Journal of the Neurological Sciences 388 (2018): 150-154.

[195]

Y. Ding, H. Q. Dong, “A Novel SLC20A2 Mutation Associated With Familial Idiopathic Basal Ganglia Calcification and Analysis of the Genotype-Phenotype Association in Chinese Patients,” Chinese Medical Journal 131 (2018): 799-803.

[196]

H. Jin, C. St Hilaire, Y. Huang, et al., “Increased Activity of TNAP Compensates for Reduced Adenosine Production and Promotes Ectopic Calcification in the Genetic Disease ACDC,” Science Signaling 9 (2016): ra121.

[197]

P. Ciceri, E. Volpi, I. Brenna, et al., “Combined Effects of Ascorbic Acid and Phosphate on Rat VSMC Osteoblastic Differentiation,” Nephrology, Dialysis, Transplantation 27 (2012): 122-127.

[198]

N. W. Chavkin, J. J. Chia, M. H. Crouthamel, and C. M. Giachelli, “Phosphate Uptake-Independent Signaling Functions of the Type III Sodium-Dependent Phosphate Transporter, PiT-1, in Vascular Smooth Muscle Cells,” Experimental Cell Research 333 (2015): 39-48.

[199]

K. Ma, P. Liu, T. Al-Maghout, et al., “Phosphate-Induced ORAI1 Expression and Store-Operated Ca2+ Entry in Aortic Smooth Muscle Cells,” Journal of Molecular Medicine 97 (2019): 1465-1475.

[200]

L. Liu, Y. Liu, Y. Zhang, et al., “High Phosphate-Induced Downregulation of PPARγ Contributes to CKD-Associated Vascular Calcification,” Journal of Molecular and Cellular Cardiology 114 (2018): 264-275.

[201]

T. Zhang, “Moscatilin Inhibits Vascular Calcification by Activating IL13RA2-Dependent Inhibition of STAT3 and Attenuating the WNT3/β-Catenin Signalling Pathway,” Journal of Advanced Research 68 (2025): 445-457.

[202]

Y. Aierken, H. He, R. Li, et al., “Inhibition of Slc39a14/Slc39a8 Reduce Vascular Calcification via Alleviating Iron Overload Induced Ferroptosis in Vascular Smooth Muscle Cells,” Cardiovascular Diabetology 23 (2024): 186.

[203]

P. Ciceri, F. Elli, P. Braidotti, et al., “Iron Citrate Reduces High Phosphate-Induced Vascular Calcification by Inhibiting Apoptosis,” Atherosclerosis 254 (2016): 93-101.

[204]

H. Rahabi-Layachi, R. Ourouda, A. Boullier, Z. A. Massy, and C. Amant, “Distinct Effects of Inorganic Phosphate on Cell Cycle and Apoptosis in Human Vascular Smooth Muscle Cells,” Journal of Cellular Physiology 230 (2015): 347-355.

[205]

L. Ho, Y. Chen, T. Wu, et al., “Phosphate Burden Induces Vascular Calcification Through a NLRP3-Caspase-1-Mediated Pyroptotic Pathway,” Life Sciences 332 (2023): 122123.

[206]

X. Dai, M. Zhao, Y. Cai, et al., “Phosphate-Induced Autophagy Counteracts Vascular Calcification by Reducing Matrix Vesicle Release,” Kidney International 83 (2013): 1042-1051.

[207]

Y. Ye, A. Chen, L. Li, et al., “Repression of the Antiporter SLC7A11/Glutathione/Glutathione Peroxidase 4 Axis Drives Ferroptosis of Vascular Smooth Muscle Cells to Facilitate Vascular Calcification,” Kidney International 102 (2022): 1259-1275.

[208]

P. Ciceri, M. Falleni, D. Tosi, et al., “Therapeutic Effect of Iron Citrate in Blocking Calcium Deposition in High Pi-Calcified VSMC: Role of Autophagy and Apoptosis,” International Journal of Molecular Sciences 20 (2019): 5925.

[209]

B. Son, K. Kozaki, K. Iijima, et al., “Statins Protect Human Aortic Smooth Muscle Cells From Inorganic Phosphate-Induced Calcification by Restoring gas6-axl Survival Pathway,” Circulation Research 9 (2006): 1024-1031.

[210]

W. Zhou, Q. Feng, M. Cheng, et al., “LncRNA H19 Sponges miR-103-3p to Promote the High Phosphorus-Induced Osteoblast Phenotypic Transition of Vascular Smooth Muscle Cells by Upregulating Runx2,” Cell Signalling 91 (2022): 110220.

[211]

J. Song, M. Liu, Y. Ma, et al., “Inflammation-Associated Ectopic Mineralization,” Fundamental Research 3 (2022): 1025-1038.

[212]

J. Martínez-Moreno, C. Herencia, A. de Oca, et al., “High Phosphate Induces a Pro-Inflammatory Response by Vascular Smooth Muscle Cells and Modulation by Vitamin D Derivatives,” Clinical Science 131 (2017): 1449-1463.

[213]

F. Macrì, I. Vigorito, S. Castiglione, et al., “High Phosphate-Induced JAK-STAT Signalling Sustains Vascular Smooth Muscle Cell Inflammation and Limits Calcification,” Biomolecules 14 (2023): 29.

[214]

N. T. Nguyen, T. T. Nguyen, D. Da Ly, et al., “Oxidative Stress by Ca2+ Overload Is Critical for Phosphate-Induced Vascular Calcification,” American Journal of Physiology Heart and Circulatory Physiology 319 (2020): H1302-H1312.

[215]

R. Jimbo, F. Kawakami-Mori, S. Mu, et al., “Fibroblast Growth Factor 23 Accelerates Phosphate-Induced Vascular Calcification in the Absence of Klotho Deficiency,” Kidney International 85 (2014): 1103-1111.

[216]

D. Zhu, N. C. Mackenzie, J. L. Millan, C. Farquharson, and V. E. MacRae, “A Protective Role for FGF-23 in Local Defence Against Disrupted Arterial Wall Integrity?,” Molecular and Cellular Endocrinology 372 (2013): 1-11.

[217]

A. K. Ajay, L. Zhu, L. Zhao, et al., “Local Vascular Klotho Mediates Diabetes-Induced Atherosclerosis via ERK1/2 and PI3-Kinase-Dependent Signaling Pathways,” Atherosclerosis 396 (2024): 118531.

[218]

J. Kendrick, M. Chonchol, “The Role of Phosphorus in the Development and Progression of Vascular Calcification,” American Journal of Kidney Diseases 58 (2011): 826-834.

[219]

F. J. Dickson, J. A. Sayer, “Nephrocalcinosis: A Review of Monogenic Causes and Insights They Provide Into this Heterogeneous Condition,” International Journal of Molecular Sciences 21 (2020): 369.

[220]

L. Shavit, P. Jaeger, R. J. Unwin, “What Is Nephrocalcinosis?,” Kidney International 88 (2015): 35-43.

[221]

B. Oliveira, R. Kleta, D. Bockenhauer, and S. B. Walsh, “Genetic, Pathophysiological, and Clinical Aspects of Nephrocalcinosis,” American Journal of Physiology Renal Physiology 311 (2016): F1243-1252.

[222]

T. Wiech, H. Hopfer, A. Gaspert, et al., “Histopathological Patterns of Nephrocalcinosis: A Phosphate Type Can be Distinguished From a Calcium Type,” Nephrology, Dialysis, Transplantation 27 (2012): 1122-1131.

[223]

P. Evenepoel, K. Daenen, B. Bammens, et al., “Microscopic Nephrocalcinosis in Chronic Kidney Disease Patients,” Nephrology, Dialysis, Transplantation 30 (2015): 843-848.

[224]

J. A. Sayer, G. Carr, N. L. Simmons, “Nephrocalcinosis: Molecular Insights Into Calcium Precipitation Within the Kidney,” Clinical Science 106 (2004): 549-561.

[225]

E. C. Heher, S. O. Thier, H. Rennke, and B. D. Humphreys, “Adverse Renal and Metabolic Effects Associated With Oral Sodium Phosphate Bowel Preparation,” Clinical Journal American Society of Nephrology 3 (2008): 1494-1503.

[226]

G. S. Markowitz, S. H. Nasr, P. Klein, et al., “Renal Failure Due to Acute Nephrocalcinosis Following Oral Sodium Phosphate Bowel Cleansing,” Human Pathology 35 (2004): 675-684.

[227]

L. Mo, L. Liaw, A. P. Evan, A. J. Sommer, J. C. Lieske, X. Wu, “Renal Calcinosis and Stone Formation in Mice Lacking Osteopontin, Tamm-Horsfall Protein, or Both,” American Journal of Physiology Renal Physiology 293 (2007): F1935-1943.

[228]

N. J. Paloian, E. M. Leaf, C. M. Giachelli, “Osteopontin Protects Against High Phosphate-Induced Nephrocalcinosis and Vascular Calcification,” Kidney International 89 (2016): 1027-1036.

[229]

J. R. Stubbs, S. Zhang, K. P. Jansson, et al., “Critical Role of Osteopontin in Maintaining Urinary Phosphate Solubility in CKD,” Kidney360 3 (2022): 1578-1589.

[230]

F. Anglani, L. Gianesello, L. Beara-Lasic, and J. Lieske, “Dent Disease: A Window Into Calcium and Phosphate Transport,” Journal of Cellular and Molecular Medicine 23 (2019): 7132-7142.

[231]

A. Rajagopal, D. Braslavsky, J. T. Lu, et al., “Exome Sequencing Identifies a Novel Homozygous Mutation in the Phosphate Transporter SLC34A1 in Hypophosphatemia and Nephrocalcinosis,” Journal of Clinical Endocrinology and Metabolism 99 (2014): E2451-E2456.

[232]

C. Bergwitz, K. I. Miyamoto, “Hereditary Hypophosphatemic Rickets With Hypercalciuria: Pathophysiology, Clinical Presentation, Diagnosis and Therapy,” Pflugers Archiv: European Journal of Physiology 471 (2019): 149-163.

[233]

S. B. Anderson, “Corneal Calcification After Amniotic Membrane Transplantation,” British Journal of Ophthalmology 87 (2003): 587-591.

[234]

K. H. Chen, W. T. Cheng, M. J. Li, and S. Y. Lin, “Corneal Calcification: Chemical Composition of Calcified Deposit,” Graefes Archive for Clinical and Experimental Ophthalmology 244 (2006): 407-410.

[235]

M. Z. Popiela, N. Hawksworth, “Corneal Calcification and Phosphates: Do You Need to Prescribe Phosphate Free?,” Journal of Ocular Pharmacology and Therapeutics 30 (2014): 800-802.

[236]

S. Kompa, C. Redbrake, B. Dunkel, A. Weber, and N. Schrage, “Corneal Calcification After Chemical Eye Burns Caused by Eye Drops Containing Phosphate Buffer,” Burns 32 (2006): 744-747.

[237]

W. Bernauer, M. A. Thiel, M. Kurrer, et al., “Corneal Calcification Following Intensified Treatment With Sodium Hyaluronate Artificial Tears,” British Journal of Ophthalmology 90 (2006): 285-288.

[238]

N. F. Schrage, S. S. Abu, L. Hermanns, C. Panfil, and R. M. Dutescu, “Irrigation With Phosphate-Buffered Saline Causes Corneal Calcification During Treatment of Ocular Burns,” Burns 45 (2019): 1871-1879.

[239]

H. Ababneh, A. Tóth, G. Lente, et al., “High Phosphate and Calcium Induce Osteoblastic Phenotype Switching and Calcification of Corneal Epithelial Cells in a Runx2-Dependent and Synergistic Manner; a Possible Mechanism of Chronic Kidney Disease-Associated Corneal Calcification,” Biochimica et Biophysica Acta - Molecular Basis of Disease 1870 (2024): 167171.

[240]

A. J. Sheppard, S. S. Paravastu, F. Farhadi, et al., “Structural and Molecular Imaging-Based Characterization of Soft Tissue and Vascular Calcification in Hyperphosphatemic Familial Tumoral Calcinosis,” Journal of Bone and Mineral Research 39 (2024): 1327-1339.

[241]

J. Huang, L. G. Cao, T. R. Zhang, S. M. Li, and Q. Q. Meng, “Primary Hyperphosphatemic Tumoral Calcinosis: A Case Report,” Osteoporosis International 33 (2022): 309-312.

[242]

D. Claramunt-Taberner, A. Bertholet-Thomas, M. Carlier, et al., “Hyperphosphatemic Tumoral Calcinosis Caused by FGF23 Compound Heterozygous Mutations: What Are the Therapeutic Options for a Better Control of Phosphatemia?,” Pediatric Nephrology 33 (2018): 1263-1267.

[243]

M. S. Ramnitz, P. Gourh, R. Goldbach-Mansky, et al., “Phenotypic and Genotypic Characterization and Treatment of a Cohort with Familial Tumoral Calcinosis/Hyperostosis-Hyperphosphatemia Syndrome,” Journal of Bone and Mineral Research 31 (2016): 1845-1854.

[244]

M. Guerra, T. Videira, D. de Fonseca, R. Vieira, J. dos Santos, S. Pinto, “Hyperphosphataemic Familial Tumoral Calcinosis: Case Report of a Rare and Challenging Disease,” Scandinavian Journal of Rheumatology 49 (2020): 80-81.

[245]

M. Chakhtoura, M. Ramnitz, N. Khoury, et al., “Hyperphosphatemic Familial Tumoral Calcinosis Secondary to Fibroblast Growth Factor 23 (FGF23) Mutation: A Report of Two Affected Families and Review of the Literature,” Osteoporosis International 29 (2018): 1987-2009.

[246]

A. M. Boyce, A. E. Lee, K. L. Roszko, and R. I. Gafni, “Hyperphosphatemic Tumoral Calcinosis: Pathogenesis, Clinical Presentation, and Challenges in Management,” Frontiers in Endocrinology 11 (2020): 293.

[247]

N. Ito, S. Fukumoto, “Congenital Hyperphosphatemic Conditions Caused by the Deficient Activity of FGF23,” Calcified Tissue International 108 (2021): 104-115.

[248]

P. T. Goldenstein, P. D. Neves, B. E. Balbo, et al., “Dialysis as a Treatment Option for a Patient with Normal Kidney Function and Familial Tumoral Calcinosis Due to a Compound Heterozygous FGF23 Mutation,” American Journal of Kidney Diseases 72 (2018): 457-461.

[249]

E. Sprecher, “Familial Tumoral Calcinosis: From Characterization of a Rare Phenotype to the Pathogenesis of Ectopic Calcification,” Journal of Investigative Dermatology 130 (2010): 652-660.

[250]

T. O. Carpenter, B. K. Ellis, K. L. Insogna, W. M. Philbrick, J. Sterpka, R. Shimkets, “Fibroblast Growth Factor 7: An Inhibitor of Phosphate Transport Derived From Oncogenic Osteomalacia-Causing Tumors,” Journal of Clinical Endocrinology and Metabolism 90 (2005): 1012-1020.

[251]

I. Chefetz, K. Kohno, H. Izumi, J. Uitto, G. Richard, E. Sprecher, “GALNT3, a Gene Associated With Hyperphosphatemic Familial Tumoral Calcinosis, Is Transcriptionally Regulated by Extracellular Phosphate and Modulates Matrix Metalloproteinase Activity,” Biochimica et Biophysica Acta 1792 (2009): 61-67.

[252]

L. Frappart, M. Boudeulle, J. Boumendil, et al., “Structure and Composition of Microcalcifications in Benign and Malignant Lesions of the Breast: Study by Light Microscopy, Transmission and Scanning Electron Microscopy, Microprobe Analysis, and X-Ray Diffraction,” Human Pathology 15 (1984): 880-889.

[253]

P. Henrot, A. Leroux, C. Barlier, and P. Génin, “Breast Microcalcifications: The Lesions in Anatomical Pathology,” Diagnostic and Interventional Imaging 95 (2014): 141-152.

[254]

M. P. Morgan, M. M. Cooke, P. A. Christopherson, P. R. Westfall, and G. M. McCarthy, “Calcium Hydroxyapatite Promotes Mitogenesis and Matrix Metalloproteinase Expression in Human Breast Cancer Cell Lines,” Molecular Carcinogenesis 32 (2001): 111-117.

[255]

M. A. Lacerda-Abreu, T. Russo-Abrahão, N. Rocco-Machado, et al., “Hydrogen Peroxide Generation as an Underlying Response to High Extracellular Inorganic Phosphate (Pi) in Breast Cancer Cells,” International Journal of Molecular Sciences 22 (2021): 10096.

[256]

R. F. Cox, A. Hernandez-Santana, S. Ramdass, G. McMahon, J. H. Harmey, M. P. Morgan, “Microcalcifications in Breast Cancer: Novel Insights Into the Molecular Mechanism and Functional Consequence of Mammary Mineralisation,” British Journal of Cancer 106 (2012): 525-537.

[257]

T. Kirsch, “Determinants of Pathological Mineralization,” Current Opinion in Rheumatology 18 (2006): 174-180.

[258]

R. F. Cox, M. P. Morgan, “Microcalcifications in Breast Cancer: Lessons From Physiological Mineralization,” Bone 53 (2013): 437-450.

[259]

M. Scimeca, E. Giannini, C. Antonacci, C. A. Pistolese, L. G. Spagnoli, E. Bonanno, “Microcalcifications in Breast Cancer: An Active Phenomenon Mediated by Epithelial Cells With Mesenchymal Characteristics,” BMC Cancer 14 (2014): 286.

[260]

W. Zhang, M. Doherty, T. Bardin, et al., “European League Against Rheumatism Recommendations for Calcium Pyrophosphate Deposition. Part I: Terminology and Diagnosis,” Annals of the Rheumatic Diseases 70 (2011): 563-570.

[261]

A. Abhishek, S. K. Tedeschi, T. Pascart, et al., “The 2023 ACR/EULAR Classification Criteria for Calcium Pyrophosphate Deposition Disease,” Arthritis Rheumatology 75 (2023): 1703-1713.

[262]

J. Miksanek, A. K. Rosenthal, “Imaging of Calcium Pyrophosphate Deposition Disease,” Current Rheumatology Reports 17 (2015): 20.

[263]

A. K. Rosenthal, L. M. Ryan, “Calcium Pyrophosphate Deposition Disease,” New England Journal of Medicine 374 (2016): 2575-2584.

[264]

F. Oliviero, C. Baggio, M. Favero, et al., “Synovial Fluid From Patients With Osteoarthritis Shows Different Inflammatory Features Depending on the Presence of Calcium Pyrophosphate Crystals,” International Journal of Molecular Sciences 25 (2023): 393.

[265]

K. Parperis, E. Papachristodoulou, L. Kakoullis, A. K. Rosenthal, “Management of Calcium Pyrophosphate Crystal Deposition Disease: A Systematic Review,” Seminars in Arthritis and Rheumatism 51 (2021): 84-94.

[266]

S. M. Iqbal, S. Qadir, H. M. Aslam, and M. A. Qadir, “Updated Treatment for Calcium Pyrophosphate Deposition Disease: An Insight,” Cureus 11 (2019): e3840.

[267]

I. Tchetverikov, L. S. Lohmander, N. Verzijl, et al., “MMP Protein and Activity Levels in Synovial Fluid From Patients With Joint Injury, Inflammatory Arthritis, and Osteoarthritis,” Annals of the Rheumatic Diseases 64 (2005): 694-698.

[268]

A. Abhishek, M. Doherty, “Pathophysiology of Articular Chondrocalcinosis—Role of ANKH,” Nature Reviews Rheumatology 7 (2011): 96-104.

[269]

K. Ryu, T. Iriuchishima, M. Oshida, et al., “The Prevalence of and Factors Related to Calcium Pyrophosphate Dihydrate Crystal Deposition in the Knee Joint,” Osteoarthritis and Cartilage 22 (2014): 975-979.

[270]

M. Reijnierse, C. Schwabl, A. Klauser, “Imaging of Crystal Disorders: Calcium Pyrophosphate Dihydrate Crystal Deposition Disease, Calcium Hydroxyapatite Crystal Deposition Disease and Gout Pathophysiology, Imaging, and Diagnosis,” Radiologic Clinics of North America 60 (2022): 641-656.

[271]

J. Yan, W. Qin, B. Xiao, et al., “Pathological Calcification in Osteoarthritis: An Outcome or a Disease Initiator?,” Biological Reviews of the Cambridge Philosophical Society 95 (2020): 960-985.

[272]

K. Davis, E. A. Imel, J. Kelley, “Hypophosphatemic Rickets and Short Stature,” Journal of Bone and Mineral Research 39 (2024): 821-825.

[273]

J. M. Pettifor, K. Thandrayen, “Hypophosphatemic Rickets: Unraveling the Role of FGF23,” Calcified Tissue International 91 (2012): 297-306.

[274]

K. E. White, G. Carn, B. Lorenz-Depiereux, A. Benet-Pages, T. M. Strom, M. J. Econs, “Autosomal-Dominant Hypophosphatemic Rickets (ADHR) Mutations Stabilize FGF-23,” Kidney International 60 (2001): 2079-2086.

[275]

G. Courbon, D. Kentrup, J. J. Thomas, et al., “FGF23 Directly Inhibits Osteoprogenitor Differentiation in Dmp1-Knockout Mice,” JCI Insight 8 (2023): e156850.

[276]

T. Liu, J. Wang, X. Xie, et al., “DMP1 Ablation in the Rabbit Results in Mineralization Defects and Abnormalities in Haversian Canal/Osteon Microarchitecture,” Journal of Bone and Mineral Research 34 (2019): 1115-1128.

[277]

D. Haffner, F. Emma, D. M. Eastwood, et al., “Clinical Practice Recommendations for the Diagnosis and Management of X-Linked Hypophosphataemia,” Nature Reviews Nephrology 15 (2019): 435-455.

[278]

J. Q. Feng, E. L. Clinkenbeard, B. Yuan, K. E. White, and M. K. Drezner, “Osteocyte Regulation of Phosphate Homeostasis and Bone Mineralization Underlies the Pathophysiology of the Heritable Disorders of Rickets and Osteomalacia,” Bone 54 (2013): 213-221.

[279]

M. E. Robinson, H. AlQuorain, M. Murshed, and F. Rauch, “Mineralized Tissues in Hypophosphatemic Rickets,” Pediatric Nephrology 35 (2020): 1843-1854.

[280]

S. Fukumoto, “FGF23-Related Hypophosphatemic Rickets/Osteomalacia: Diagnosis and New Treatment,” Journal of Molecular Endocrinology 66 (2021): R57-R65.

[281]

M. Yamazaki, T. Michigami, “Osteocytes and the Pathogenesis of Hypophosphatemic Rickets,” Frontiers in Endocrinology 13 (2022): 1005189.

[282]

Y. Kinoshita, T. Saito, Y. Shimizu, et al., “Mutational Analysis of Patients With FGF23-Related Hypophosphatemic Rickets,” European Journal of Endocrinology 167 (2012): 165-172.

[283]

S. K. Murali, O. Andrukhova, E. L. Clinkenbeard, K. E. White, and R. G. Erben, “Excessive Osteocytic Fgf23 Secretion Contributes to Pyrophosphate Accumulation and Mineralization Defect in Hyp Mice,” PLoS Biology 14 (2016): e1002427.

[284]

H. Li, Y. Jing, R. Zhang, et al., “Hypophosphatemic Rickets Accelerate Chondrogenesis and Cell Trans-Differentiation From TMJ Chondrocytes Into Bone Cells via a Sharp Increase in β-Catenin,” Bone 131 (2020): 115151.

[285]

Y. Sabbagh, T. O. Carpenter, M. B. Demay, “Hypophosphatemia Leads to Rickets by Impairing Caspase-Mediated Apoptosis of Hypertrophic Chondrocytes,” Proceedings National Academy of Science USA 102 (2005): 9637-9642.

[286]

C. Liu, X. Ni, Z. Zhao, et al., “Bone Characteristics of Autosomal Dominant Hypophosphatemic Rickets Patients,” Bone 167 (2023): 116602.

[287]

T. Hayashibara, T. Hiraga, A. Sugita, et al., “Regulation of Osteoclast Differentiation and Function by Phosphate: Potential Role of Osteoclasts in the Skeletal Abnormalities in Hypophosphatemic Conditions,” Journal of Bone and Mineral Research 22 (2007): 1743-1751.

[288]

L. E. Cole, T. Vargo-Gogola, R. K. Roeder, “Targeted Delivery to Bone and Mineral Deposits Using Bisphosphonate Ligands,” Advanced Drug Delivery Reviews 99 (2016): 12-27.

[289]

S. Cremers, P. Garnero, “Biochemical Markers of Bone Turnover in the Clinical Development of Drugs for Osteoporosis and Metastatic Bone Disease: Potential Uses and Pitfalls,” Drugs 66 (2006): 2031-2058.

[290]

J. S. Barbosa, F. A. Almeida Paz, S. S. Braga, “Old Friends of Bones and New Trends in Clinics,” Journal of Medicinal Chemistry 64 (2021): 1260-1282.

[291]

M. J. Rogers, J. C. Crockett, F. P. Coxon, and J. Mönkkönen, “Biochemical and Molecular Mechanisms of Action of Bisphosphonates,” Bone 49 (2011): 34-41.

[292]

C. A. Migliorati, J. B. Epstein, E. Abt, and J. R. Berenson, “Osteonecrosis of the Jaw and Bisphosphonates in Cancer: A Narrative Review,” Nature Reviews Endocrinology 7 (2011): 34-42.

[293]

F. Bennardo, S. Barone, A. Antonelli, and A. Giudice, “Autologous Platelet Concentrates as Adjuvant in the Surgical Management of Medication-Related Osteonecrosis of the Jaw,” Periodontology 2000 97 (2024): 287-307.

[294]

S. M. Sprague, K. J. Martin, D. W. Coyne, “Phosphate Balance and CKD-Mineral Bone Disease,” Kidney International Report 6 (2021): 2049-2058.

[295]

E. A. Friedman, “An Introduction to Phosphate Binders for the Treatment of Hyperphosphatemia in Patients With Chronic Kidney Disease,” Kidney International Supplement 68 (2005): S2-S6.

[296]

A. B. Pai, S. M. Jang, N. Wegrzyn, “Iron-Based Phosphate Binders - A New Element in Management of Hyperphosphatemia,” Expert Opinion on Drug Metabolism & Toxicology 12 (2015): 115-127.

[297]

D. Nastou, B. Fernández-Fernández, U. Elewa, et al., “Next-Generation Phosphate Binders: Focus on Iron-Based Binders,” Drugs 74 (2014): 863-877.

[298]

S. Brunner-Ziegler, B. Fröschl, C. Hiebinger, and J. Zsifkovits, “Effectiveness and Cost-Efficacy of Phosphate Binders in Hemodialysis,” Annals of Nutrition & Metabolism 58 (2011): 315-319.

[299]

G. I. Baroncelli and S. Mora, “X-Linked Hypophosphatemic Rickets: Multisystemic Disorder in Children Requiring Multidisciplinary Management,” Frontiers in Endocrinology 12 (2021): 688309.

[300]

D. Haffner, F. Emma, D. M. Eastwood, et al., “Clinical Practice Recommendations for the Diagnosis and Management of X-Linked Hypophosphataemia,” Nature Reviews Nephrology 15 (2019): 435-455.

[301]

O. Mäkitie, S. W. Kooh, E. Sochett, “Prolonged High-Dose Phosphate Treatment: A Risk Factor for Tertiary Hyperparathyroidism in X-Linked Hypophosphatemic Rickets,” Clinical Endocrinology 58 (2003): 163-168.

[302]

M. G. Seikaly, M. Baum, “Thiazide Diuretics Arrest the Progression of Nephrocalcinosis in Children With X-Linked Hypophosphatemia,” Pediatrics 108 (2001).

[303]

C. Qiu, Y. Wu, Q. Guo, et al., “Preparation and Application of Calcium Phosphate Nanocarriers in Drug Delivery,” Materials Today Bio 17 (2022): 100501.

[304]

K. N. Panchal, S. Mutalik, J. Manikkath, “Biomimetic Nanoparticle-Driven Strategies for Targeted Drug Delivery in Glioblastoma,” Journal of Nanoparticle Research 26 (2024): 192.

[305]

R. Zhang, P. Somasundaran, “Advances in Adsorption of Surfactants and Their Mixtures at Solid/Solution Interfaces,” Advances in Colloid and Interface Science 123-126 (2006): 213-229.

[306]

V. Sorribas, N. Guillén, C. Sosa, “Substrates and Inhibitors of Phosphate Transporters: From Experimental Tools to Pathophysiological Relevance,” Pflugers Archiv: European Journal of Physiology 471 (2019): 53-65.

[307]

A. J. King, M. Siegel, Y. He, et al., “Inhibition of Sodium/Hydrogen Exchanger 3 in the Gastrointestinal Tract by Tenapanor Reduces Paracellular Phosphate Permeability,” Science Translational Medicine 10 (2018): eaam6474.

[308]

Y. Tsuboi, S. Ohtomo, Y. Ichida, et al., “EOS789, a Novel Pan-Phosphate Transporter Inhibitor, Is Effective for the Treatment of Chronic Kidney Disease-Mineral Bone Disorder,” Kidney International 98 (2020): 343-354.

[309]

Y. Tsuboi, Y. Ichida, A. Murai, et al., “EOS789, Pan-Phosphate Transporter Inhibitor, Ameliorates the Progression of Kidney Injury in Anti-GBM-Induced Glomerulonephritis Rats,” Pharmacology Research & Perspectives 10 (2022): e00973.

[310]

K. M. Hill Gallant, E. R. Stremke, L. L. Trevino, et al., “EOS789, a Broad-Spectrum Inhibitor of Phosphate Transport, Is Safe With an Indication of Efficacy in a Phase 1b Randomized Crossover Trial in Hemodialysis Patients,” Kidney International 99 (2021): 1225-1233.

[311]

L. Wang, L. Zuo, M. Shi, et al., “A Pan-Inhibitor of Phosphate Transporters AP306 in Hemodialysis Patients,” Kidney International Report 10 (2025): 1143-1151.

[312]

V. Clerin, H. Saito, K. J. Filipski, et al., “Selective Pharmacological Inhibition of the Sodium-Dependent Phosphate Cotransporter NPT2a Promotes Phosphate Excretion,” Journal of Clinical Investigation 130 (2020): 6510-6522.

[313]

L. Thomas, J. Xue, S. K. Murali, R. A. Fenton, J. A. Dominguez Rieg, T. Rieg, “Pharmacological Npt2a Inhibition Causes Phosphaturia and Reduces Plasma Phosphate in Mice With Normal and Reduced Kidney Function,” Journal of the American Society of Nephrology 30 (2019): 2128-2139.

[314]

L. Thomas, J. Xue, V. N. Tomilin, O. M. Pochynyuk, J. A. Dominguez Rieg, T. Rieg, “PF-06869206 Is a Selective Inhibitor of Renal Pi Transport: Evidence From In Vitro and In Vivo Studies,” American Journal of Physiology Renal Physiology 319 (2020): F541-F551.

[315]

X. Wang, Y. Xu, X. Yu, et al., “Effects of Pharmacological Inhibition of the Sodium-Dependent Phosphate Cotransporter 2b (NPT2b) on Intestinal Phosphate Absorption in Mouse and Rat Models,” Pharmacology Research & Perspectives 10 (2022): e00938.

[316]

P. Lanzer, F. M. Hannan, J. D. Lanzer, et al., “Medial Arterial Calcification: JACC State-of-the-Art Review,” Journal of the American College of Cardiology 78 (2021): 1145-1165.

[317]

W. Feng, Y. Teng, Q. Zhong, et al., “Biomimetic Grapefruit-Derived Extracellular Vesicles for Safe and Targeted Delivery of Sodium Thiosulfate Against Vascular Calcification,” ACS Nano 17 (2023): 24773-24789.

[318]

T. Zhang, M. Zhu, J. Ma, et al., “Moscatilin Inhibits Vascular Calcification by Activating IL13RA2-Dependent Inhibition of STAT3 and Attenuating the WNT3/β-Catenin Signalling Pathway,” Journal of Advanced Research 68 (2025): 445-457.

[319]

H. Liu, X. Yang, K. Tang, et al., “Sulforaphane Elicts Dual Therapeutic Effects on Renal Inflammatory Injury and Crystal Deposition in Calcium Oxalate Nephrocalcinosis,” Theranostics 10 (2020): 7319-7334.

[320]

N. J. Paloian, E. M. Leaf, C. M. Giachelli, “Osteopontin Protects Against High Phosphate-Induced Nephrocalcinosis and Vascular Calcification,” Kidney International 89 (2016): 1027-1036.

[321]

H. Anders, B. Suarez-Alvarez, M. Grigorescu, et al., “The Macrophage Phenotype and Inflammasome Component NLRP3 Contributes to Nephrocalcinosis-Related Chronic Kidney Disease Independent From IL-1-Mediated Tissue Injury,” Kidney International 93 (2018): 656-669.

[322]

M. Brunkhorst, L. Brunkhorst, H. Martens, et al., “Presentation and Outcome in Carriers of Pathogenic Variants in SLC34A1 and SLC34A3 Encoding Sodium-Phosphate Transporter NPT 2a and 2c,” Kidney International 107 (2025): 116-129.

[323]

F. Lixi, B. Pintus, G. Giannaccare, “Management of Calcareous Corneal Degeneration From Medication Washout to Corneal Transplantation. Case Series and Review of the Literature,” OBM Transplantation 08 (2024): 1-11.

[324]

H. Li, M. Dong, Q. Zhou, et al., “Corneal Calcification of Acellular Porcine Corneal Stroma Following Lamellar Keratoplasty,” Acta Ophthalmologica 100 (2020): 164-174.

[325]

X. Yin, M. Wu, C. Jin, and S. Zhou, “Comparison of Photodynamic Therapy With Two Different Parameters Combined With Subconjunctival Injection of Bevacizumab for Corneal Neovascularization,” Photodiagnosis and Photodynamic Therapy 46 (2024): 104067.

[326]

J. J. Lammoglia, V. Mericq, “Familial Tumoral Calcinosis Caused by a Novel FGF23 Mutation: Response to Induction of Tubular Renal Acidosis With Acetazolamide and the Non-Calcium Phosphate Binder Sevelamer,” Hormone Research 71 (2009): 178-184.

[327]

A. Michon-Colin, E. Bouderlique, D. Prié, et al., “Successful Burosumab Treatment in an Adult Patient With X-Linked Hypophosphatemia and Chronic Kidney Disease Stage 3b,” Calcified Tissue International 114 (2024): 310-314.

[328]

V. Tiwari, A. Goyal, M. Nagar, and J. A. Santoshi, “Hyperphosphataemic Tumoral Calcinosis,” Lancet 393 (2019): 168.

[329]

Y. Peng, Z. Y. Luo, J. Ni, et al., “Precision Biopsy of Breast Microcalcifications: An Improvement in Surgical Excision,” Oncology letters 16 (2018): 1212-1218.

[330]

Y. J. Yeow, C. C. Yu, Y. C. Cheung, and S. C. Chen, “A Cohort Study of Mammography-Guided Vacuum-Assisted Breast Biopsy in Patients With Compressed Thin Breasts (≦ 3 cm),” Asian Journal of Surgery 46 (2023): 4296-4301.

[331]

K. Wang, Z. Ye, X. Xie, H. Cui, T. Chen, B. Liu, “MLN-Net: A Multi-Source Medical Image Segmentation Method for Clustered Microcalcifications Using Multiple Layer Normalization,” Knowledge Based System 283 (2024): 111127.

[332]

A. K. Rosenthal, L. M. Ryan, “Calcium Pyrophosphate Deposition Disease,” New England Journal of Medicine 374 (2016): 2575-584.

[333]

T. Pascart, A. Latourte, S. K. Tedeschi, et al., “Features Associated With Different Inflammatory Phenotypes of Calcium Pyrophosphate Deposition Disease: A Study Using Data From the International American College of Rheumatology/EULAR Calcium Pyrophosphate Deposition Classification Criteria Cohort,” Arthritis Rheumatology 76 (2024): 1780-1788.

[334]

S. Sirotti, C. Jauffret, A. Adinolfi, et al., “Pseudogout, Chondrocalcinosis, CPPD et al: Crystal Clear… or Clear as Mud?-The Time Has Come to Reconsider the Nomenclature of Calcium Pyrophosphate Deposition,” Annals of the Rheumatic Diseases S0003-4967 (2025): 00894-00895.

[335]

M. Azar, “Management of X-Linked Hypophosphatemic Rickets: A Review,” International Journal of Research in Medical Sciences 8 (2020): 3761.

[336]

T. Arcidiacono, N. E. Foligno, E. Brioni, et al., “Different Efficacy of Burosumab on Physical Performance and Serum Phosphate in Adult Patients With X-Linked Hyphophosphatemic Rickets During the First Six-Month of Treatment,” Journal of Clinical Medicine 12 (2023): 2906.

[337]

N. J. Paloian, B. Nemeth, M. Sharafinski, P. Modaff, R. D. Steiner, “Real-World Effectiveness of Burosumab in Children With X-Linked Hypophosphatemic Rickets,” Pediatric Nephrology 37 (2022): 2667-2677.

[338]

I. Almeida, A. Rodrigues, A. Costa-Rei, and M. Stone, “X-Linked Hypophosphatemic Rickets: A Pediatric Case Report,” Portuguese Journal of Nephrology & Hypertension 36 (2022): 170-174.

[339]

I. Casalin, E. Ceneri, S. Ratti, L. Manzoli, L. Cocco, M. Y. Follo, “Nuclear Phospholipids and Signaling: An Update of the Story,” Cells 13 (2024): 713.

[340]

M. Bäck, J. B. Michel, “From Organic and Inorganic Phosphates to Valvular and Vascular Calcifications,” Cardiovascular Research 117 (2021): 2016-2029.

[341]

T. M. Livermore, C. Azevedo, B. Kolozsvari, M. S. Wilson, and A. Saiardi, “Phosphate, Inositol and Polyphosphates,” Biochemical Society Transactions 44 (2016): 253-259.

[342]

M. W. Roe, J. J. Lemasters, B. Herman, “Assessment of Fura-2 for Measurements of Cytosolic Free Calcium,” Cell Calcium 11 (1990): 63-73.

[343]

M. X. Mori, Y. Imai, K. Itsuki, and R. Inoue, “Quantitative Measurement of Ca(2+)-Dependent Calmodulin-Target Binding by Fura-2 and CFP and YFP FRET Imaging in Living Cells,” Biochemistry 50 (2011): 4685-4696.

[344]

J. Zhang, Y. Ji, S. Jiang, et al., “Calcium-Collagen Coupling Is Vital for Biomineralization Schedule,” Advancement of Science 8 (2021): e2100363.

[345]

X. Guo, C. Y. Lin, S. Alavi, L. You, and J. Mostaghimi, “Investigation of Calcium Variations in Single Cells and the Impact of Yoda1 on Osteocytes by ICP-OES,” Analytica Chimica Acta 1281 (2023): 341906.

[346]

H. Huang, L. Lei, Y. Shangguan, et al., “Comprehensive Bioremediation Effect of Phosphorus-Mineralized Bacterium Enterobacter Sp. PMB-5 on Cadmium Contaminated Soil-Crop System,” Journal of Hazardous Materials 470 (2024): 134227.

[347]

K. Zhang, D. Zhang, X. Wu, and Y. Xue, “Continuous and Efficient Immobilization of Heavy Metals by Phosphate-Mineralized Bacterial Consortium,” Journal of Hazardous Materials 416 (2021): 125800.

[348]

K. Zhang, Y. Xue, J. Zhang, and X. Hu, “Removal of Lead From Acidic Wastewater by Bio-Mineralized Bacteria With pH Self-Regulation,” Chemosphere 241 (2020): 125041.

[349]

D. Peng, Y. Zhang, X. Chen, et al., “Effect of Phosphate-Mineralized Bacteria on Multi-Metals Migration Behavior in Vanadium Tailing Slags: Coexistence of Immobilization and Mobilization,” Journal of Hazardous Materials 480 (2024): 135880.

[350]

H. Huang, K. Wang, S. Li, et al., “Different Survival Strategies of the Phosphate-Mineralizing Bacterium Enterobacter Sp. PMB-5 in Response to Cadmium Stress: Biomineralization, Biosorption, and Bioaccumulation,” Journal of Hazardous Materials 465 (2024): 133284.

[351]

K. D. Morrison, M. Zavarin, A. B. Kersting, et al., “Influence of Uranium Concentration and pH on U-Phosphate Biomineralization by Caulobacter OR37,” Environmental Science & Technology 55 (2021): 1626-1636.

[352]

L. Guo, J. Ding, W. Zhou, “Converting Bacteria Into Autologous Tumor Vaccine via Surface Biomineralization of Calcium Carbonate for Enhanced Immunotherapy,” Acta Pharmaceutica Sinica B 13 (2023): 5074-5090.

[353]

C. Wang, L. Zhong, J. Xu, et al., “Oncolytic Mineralized Bacteria as Potent Locally Administered Immunotherapeutics,” Nature Biomedical Engineering 8 (2024): 561-578.

[354]

X. Chen, P. Li, B. Luo, et al., “Surface Mineralization of Engineered Bacterial Outer Membrane Vesicles to Enhance Tumor Photothermal/Immunotherapy,” ACS Nano 18 (2024): 1357-1370.

[355]

I. C. Forster, N. Hernando, J. Biber, and H. Murer, “Phosphate Transporters of the SLC20 and SLC34 Families,” Molecular Aspects of Medicine 34 (2013): 386-395.

[356]

J. Biber, N. Hernando, I. Forster, “Phosphate Transporters and Their Function,” Annual Review of Physiology 75 (2013): 535-550.

[357]

C. Xu, J. Xu, H. Tang, et al., “A Phosphate-Sensing Organelle Regulates Phosphate and Tissue Homeostasis,” Nature 617 (2023): 798-806.

[358]

C. Bergwitz, H. Jüppner, “Regulation of Phosphate Homeostasis by PTH, Vitamin D, and FGF23,” Annual Review of Medicine 61 (2010): 91-104.

[359]

M. S. Razzaque, “The FGF23-Klotho Axis: Endocrine Regulation of Phosphate Homeostasis,” Nature Reviews Endocrinology 5 (2009): 611-619.

[360]

T. Schinke, R. Oheim, “Hereditary Hypophosphatemic Rickets With Hypercalciuria (HHRH), a Complex Disorder in Need of Precision Medicine,” Kidney International 105 (2024): 927-929.

[361]

Z. Zhu, B. Bo-Ran Ho, A. Chen, et al., “An Update on Clinical Presentation and Responses to Therapy of Patients With Hereditary Hypophosphatemic Rickets With Hypercalciuria (HHRH),” Kidney International 105 (2024): 1058-1076.

[362]

M. G. Vervloet, A. J. van Ballegooijen, “Prevention and Treatment of Hyperphosphatemia in Chronic Kidney Disease,” Kidney International 93 (2018): 1060-1072.

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