Physiological and pathological/ectopic mineralization: from composition to microstructure

Abstract

Biomineralization is a process that leads to the formation of hierarchically arranged structures in mineralized tissues, such as bone and teeth. Extensive research has been conducted on the crystals in bones and teeth, with the aim of understanding the underlying mechanisms of the mineralization process. Pathological/ectopic mineralization, such as kidney stones, calcific tendinitis, and skeletal fluorosis, shares some similar features but different mechanisms to physiological mineralization. A better understanding will provide new perspectives for treating pathological/ectopic mineralization-related diseases. This review provides an overview of the mechanisms of the crystallization and growth of crystals in physiological and pathological conditions from a chemistry perspective. By linking the microstructures and functions of crystals formed in both conditions, potential approaches are proposed to treat pathological/ectopic mineralization-related diseases.

Keywords

Physiological mineralization / pathological/ectopic mineralization / apatite crystals / mineral crystallinity / dental tissues / bone remodeling

References

[1] Weiner S.An overview of biomineralization processes and the problem of the vital effect.Rev Mineral Geochem2003;54:1-29

[2] Tai K,Suresh S,Ortiz C.Nanoscale heterogeneity promotes energy dissipation in bone.Nat Mater2007;6:454-62

[3] Lichtenegger HC,Bartl MH,Stucky GD.High abrasion resistance with sparse mineralization: copper biomineral in worm jaws.Science2002;298:389-92

[4] Hamm CE,Springer O.Architecture and material properties of diatom shells provide effective mechanical protection.Nature2003;421:841-3

[5] Tommasini SM,Hof PR.Percolation theory relates corticocancellous architecture to mechanical function in vertebrae of inbred mouse strains.Bone2008;42:743-50 PMCID:PMC2650241

[6] Murat D,Bertinetti L.The magnetosome membrane protein, MmsF, is a major regulator of magnetite biomineralization in Magnetospirillum magneticum AMB-1.Mol Microbiol2012;85:684-99 PMCID:PMC3570065

[7] Gautron J,Le Roy N,Rodriguez-Navarro AB.Avian eggshell biomineralization: an update on its structure, mineralogy and protein tool kit.BMC Mol Cell Biol2021;22:11

[8] Ramos-Silva P,Le Roy N.Novel molluskan biomineralization proteins retrieved from proteomics: a case study with Upsalin.Chembiochem2012;13:1067-78

[9] Beniash E,Margolis HC.Structural changes in amelogenin upon self-assembly and mineral interactions.J Dent Res2012;91:967-72 PMCID:PMC3446832

[10] Hosseini S,Mountassif D,Vali H.C-terminal amidation of an osteocalcin-derived peptide promotes hydroxyapatite crystallization.J Biol Chem2013;288:7885-93 PMCID:PMC3597826

[11] Weiner S.The material bone: structure-mechanical function relations.Annu Rev Mater Sci1998;28:271-98

[12] Kokubo T.How useful is SBF in predicting in vivo bone bioactivity?.Biomaterials2006;27:2907-15

[13] Taehoon J,Eunkyung K.Analysis of microstructure in mouse femur and decalcification effect on microstructure by electron microscopy.J Anal Sci Technol2010;1:124-9Available from: https://www.researchgate.net/publication/49587402_Analysis_of_microstructure_in_mouse_femur_and_decalcification_effect_on_microstructure_by_electron_microscopy [Last accessed on 5 July 2023].

[14] Takadama H,Kokubo T.TEM-EDX study of mechanism of bonelike apatite formation on bioactive titanium metal in simulated body fluid.J Biomed Mater Res2001;57:441-8

[15] Baino F.The use of simulated body fluid (SBF) for assessing materials bioactivity in the context of tissue engineering: review and challenges.Biomimetics2020;5:57 PMCID:PMC7709622

[16] Suchý T,Sedláček R.Various simulated body fluids lead to significant differences in collagen tissue engineering scaffolds.Materials2021;14:4388 PMCID:PMC8399520

[17] Bonfiglio R,Urbano N,Schillaci O.Breast microcalcifications: biological and diagnostic perspectives.Future Oncol2018;14:3097-9

[18] Busing CM,Menges V.Differences in microcalcification in breast tumors.Virchows Arch A1981;393:307-13

[19] Barman I,Saha A.Application of Raman spectroscopy to identify microcalcifications and underlying breast lesions at stereotactic core needle biopsy.Cancer Res2013;73:3206-15 PMCID:PMC3754785

[20] Tsolaki E.Pathological mineralization: the potential of mineralomics.Materials2019;12:3126 PMCID:PMC6804219

[21] Tan ACS,Fearn S.Calcified nodules in retinal drusen are associated with disease progression in age-related macular degeneration.Sci Transl Med2018;10:eaat4544

[22] Kirsch T.Determinants of pathological mineralization.Curr Opin Rheumatol2006;18:174-80

[23] Reznikov N,Fratzl P.A materials science vision of extracellular matrix mineralization.Nat Rev Mater2016;1:16041

[24] Luo G,McKee MD.Spontaneous calcification of arteries and cartilage in mice lacking matrix GLA protein.Nature1997;386:78-81

[25] Yagami K,Enomoto-Iwamoto M.Matrix GLA protein is a developmental regulator of chondrocyte mineralization and, when constitutively expressed, blocks endochondral and intramembranous ossification in the limb.J Cell Biol1999;147:1097-108 PMCID:PMC2169349

[26] Yuan FL,Ye JX,Ren LJ.Apoptotic bodies from endplate chondrocytes enhance the oxidative stress-induced mineralization by regulating PPi metabolism.J Cell Mol Med2019;23:3665-75 PMCID:PMC6484318

[27] Wu LN,Dunkelberger DG,Concannon B.Physicochemical characterization of the nucleational core of matrix vesicles.J Biol Chem1997;272:4404-11

[28] Sekaran S,Thangavelu L.The physiological and pathological role of tissue nonspecific alkaline phosphatase beyond mineralization.Biomolecules2021;11:1564 PMCID:PMC8615537

[29] Franklin BS,Latz E.Crystal formation in inflammation.Annu Rev Immunol2016;34:173-202

[30] Poloni LN.The materials science of pathological crystals.Chem Mater2014;26:477-95

[31] Bazin D,Combes C.Characterization and some physicochemical aspects of pathological microcalcifications.Chem Rev2012;112:5092-120

[32] Ralph D,Uitto J.Inorganic pyrophosphate deficiency syndromes and potential treatments for pathologic tissue calcification.Am J Pathol2022;192:762-70 PMCID:PMC9088198

[33] Singh A,Tandon C.An update on vascular calcification and potential therapeutics.Mol Biol Rep2021;48:887-96

[34] Fuery MA,Kaplan FS.Vascular ossification: pathology, mechanisms, and clinical implications.Bone2018;109:28-34

[35] Durham AL,Scatena M,Shanahan CM.Role of smooth muscle cells in vascular calcification: implications in atherosclerosis and arterial stiffness.Cardiovasc Res2018;114:590-600 PMCID:PMC5852633

[36] Vidavsky N,Estroff LA.Multiple pathways for pathological calcification in the human body.Adv Healthc Mater2021;10:e2001271 PMCID:PMC8724004

[37] Cazalbou S,Eichert D.Adaptative physico-chemistry of bio-related calcium phosphates.J Mater Chem2004;14:2148-53

[38] Zipkin I.The inorganic composition of bones and teeth. In: Schraer H, editor. Biological calcification: cellular and molecular aspects. Boston: Springer; 1970. pp. 69-103.

[39] Elsharkawy S.Hierarchical biomineralization: from nature’s designs to synthetic materials for regenerative medicine and dentistry.Adv Healthc Mater2018;7:e1800178

[40] Abou Neel EA,Strange A.Demineralization-remineralization dynamics in teeth and bone.Int J Nanomed2016;11:4743-63 PMCID:PMC5034904

[41] Eanes ED,Posner AS.Intermediate states in the precipitation of hydroxyapatite.Nature1965;208:365-7

[42] Habraken W,Epple M.Calcium phosphates in biomedical applications: materials for the future?.Mater Today2016;19:69-87

[43] Beniash E,Lam RS.Transient amorphous calcium phosphate in forming enamel.J Struct Biol2009;166:133-43 PMCID:PMC2731811

[44] Mahamid J,Shimoni E.Mapping amorphous calcium phosphate transformation into crystalline mineral from the cell to the bone in zebrafish fin rays.Proc Natl Acad Sci USA2010;107:6316-21 PMCID:PMC2851957

[45] Termine JD.Infrared analysis of rat bone: age dependency of amorphous and crystalline mineral fractions.Science1966;153:1523-5

[46] Habraken WJ,Brylka LJ.Ion-association complexes unite classical and non-classical theories for the biomimetic nucleation of calcium phosphate.Nat Commun2013;4:1507

[47] Brown WE,Ferris JS.Interlayering of crystalline octacalcium phosphate and hydroxylapatite.J Phys Chem1979;83:1385-8

[48] Wang Y,Fernandes FM.Water-mediated structuring of bone apatite.Nat Mater2013;12:1144-53

[49] Rey C.What bridges mineral platelets of bone?.Bonekey Rep2014;3:586 PMCID:PMC4230188

[50] Dorvee JR.Water in the formation of biogenic minerals: peeling away the hydration layers.J Struct Biol2013;183:278-303 PMCID:PMC3938164

[51] Becker RO,Berg EW.The trace elements of human bone.J Bone Joint Surg Am1968;50:326-34

[52] Ellis EH,Becker RO.Trace elements in tendon collagen.Clin Orthop Relat Res1969;65:195-8Available from: https://www.robertobecker.net/PDFs/BF050-CORR1969.pdf [Last accessed on 5 July 2023].

[53] Grynpas MD.The effect of fluoride treatment on bone mineral crystals in the rat.Bone1992;13:423-9

[54] Ressler A,Ivanišević I,Ivanković H.Ionic substituted hydroxyapatite for bone regeneration applications: a review, Open Ceram 2021;6:100122.

[55] Legros R,Bonel G.Age-related changes in mineral of rat and bovine cortical bone.Calcif Tissue Int1987;41:137-44

[56] Handschin RG.Crystallographic and chemical analysis of human bone apatite (Crista Iliaca).Clin Rheumatol1994;13 Suppl 1:75-90

[57] Yao X,Kettle AD,Phillips CL.Gender-dependence of bone structure and properties in adult osteogenesis imperfecta murine model.Ann Biomed Eng2013;41:1139-49 PMCID:PMC3703620

[58] Nelson DG.The influence of carbonate on the atomic structure and reactivity of hydroxyapatite.J Dent Res1981;60 Spec No C:1621-9

[59] Farlay D,Rey C,Boivin G.Mineral maturity and crystallinity index are distinct characteristics of bone mineral.J Bone Miner Metab2010;28:433-45 PMCID:PMC2958843

[60] Lacruz RS,Wright JT.Dental enamel formation and implications for oral health and disease.Physiol Rev2017;97:939-93 PMCID:PMC6151498

[61] Akiva A,Masic A.On the pathway of mineral deposition in larval zebrafish caudal fin bone.Bone2015;75:192-200

[62] Bennet M,Faivre D.Simultaneous Raman microspectroscopy and fluorescence imaging of bone mineralization in living zebrafish larvae.Biophys J2014;106:L17-9 PMCID:PMC3944822

[63] Crane NJ,Morris MD,Ignelzi MA Jr.Raman spectroscopic evidence for octacalcium phosphate and other transient mineral species deposited during intramembranous mineralization.Bone2006;39:434-42

[64] Simon P,Worch H.First evidence of octacalcium phosphate@osteocalcin nanocomplex as skeletal bone component directing collagen triple-helix nanofibril mineralization.Sci Rep2018;8:13696 PMCID:PMC6135843

[65] Nudelman F,Sommerdijk NA.In vitro models of collagen biomineralization.J Struct Biol2013;183:258-69

[66] Olszta MJ,Jee SS.Bone structure and formation: a new perspective.Mater Sci Eng R Rep2007;58:77-116

[67] George A.Phosphorylated proteins and control over apatite nucleation, crystal growth, and inhibition.Chem Rev2008;108:4670-93 PMCID:PMC2748976

[68] Gower LB.Biomimetic model systems for investigating the amorphous precursor pathway and its role in biomineralization.Chem Rev2008;108:4551-627 PMCID:PMC3652400

[69] de Jonge LT, van den Beucken JJ, Leeuwenburgh SC, Hamers AA, Wolke JG, Jansen JA. In vitro responses to electrosprayed alkaline phosphatase/calcium phosphate composite coatings.Acta Biomater2009;5:2773-82

[70] Omelon SJ.Relationships between polyphosphate chemistry, biochemistry and apatite biomineralization.Chem Rev2008;108:4694-715

[71] Fleisch H.Isolation from urine of pyrophosphate, a calcification inhibitor.Am J Physiol1962;203:671-5

[72] Cuy JL,Livi KJ,Weihs TP.Nanoindentation mapping of the mechanical properties of human molar tooth enamel.Arch Oral Biol2002;47:281-91

[73] Tjäderhane L,Breschi L,Pashley DH.Dentin basic structure and composition-an overview.Endod Topics2009;20:3-29

[74] Linde A.Dentin mineralization and the role of odontoblasts in calcium transport.Connect Tissue Res1995;33:163-70

[75] Hao J,George A.Temporal and spatial localization of the dentin matrix proteins during dentin biomineralization.J Histochem Cytochem2009;57:227-37 PMCID:PMC2664930

[76] Chatzistavrou X,Ma PX.Innovative approaches to regenerate enamel and dentin.Int J Dent2012;2012:856470 PMCID:PMC3359805

[77] Vieira AP,Limeback H,Grynpas MD.Is fluoride concentration in dentin and enamel a good indicator of dental fluorosis?.J Dent Res2004;83:76-80

[78] White SN,Paine ML,Sarikaya M.Biological organization of hydroxyapatite crystallites into a fibrous continuum toughens and controls anisotropy in human enamel.J Dent Res2001;80:321-6

[79] Giacaman R,Carrera C.5 - Mineralization processes in hard tissues: teeth. In: Biomineralization and biomaterials. Amsterdam, The Netherlands: Elsevier; 2016. pp. 147-85.

[80] Wang L,Du C,Nancollas GH.Amelogenin promotes the formation of elongated apatite microstructures in a controlled crystallization system.J Phys Chem C Nanomater Interfaces2007;111:6398-404 PMCID:PMC2843430

[81] Robinson C,Brookes SJ,Shore RC.The chemistry of enamel development.Int J Dev Biol1995;39:145-52

[82] Smith CE.Cellular and chemical events during enamel maturation.Crit Rev Oral Biol Med1998;9:128-61

[83] Moradian-Oldak J.Protein-mediated enamel mineralization.Front Biosci2012;17:1996-2023 PMCID:PMC3442115

[84] Yamamoto T,Yamamoto T,Amizuka N.Histology of human cementum: its structure, function, and development.Jpn Dent Sci Rev2016;52:63-74 PMCID:PMC5390338

[85] Gonçalves PF,Sallum AW,Toledo S.Dental cementum reviewed: development, structure, composition, regeneration and potential functions.Braz J Oral Sci2005;4:651-8Available from: https://periodicos.sbu.unicamp.br/ojs/index.php/bjos/article/view/8641790 [Last accessed on 5 July 2023].

[86] Neiders ME,Miller WA.Electron probe microanalysis of cementum and underlying dentin in young permanent teeth.J Dent Res1972;51:122-30

[87] Nakagaki H,Strong M.Distribution of fluoride in human cementum.Arch Oral Biol1985;30:101-4

[88] Andras NL,Chu EY.Between a rock and a hard place: regulation of mineralization in the periodontium.Genesis2022;60:e23474 PMCID:PMC9492628

[89] Foster BL,Somerman MJ.Development and structure of cementum. In: Naji S, Rendu W, Gourichon L, editors. Dental cementum in anthropology. Cambridge: Cambridge University Press; 2022. pp. 46-64.

[90] Lundberg YW,Thiessen KD.Mechanisms of otoconia and otolith development.Dev Dyn2015;244:239-53 PMCID:PMC4482761

[91] Zhao X,Yamoah EN.Gene targeting reveals the role of Oc90 as the essential organizer of the otoconial organic matrix.Dev Biol2007;304:508-24 PMCID:PMC1950278

[92] Thompson RB,Bundy JG.Identification of hydroxyapatite spherules provides new insight into subretinal pigment epithelial deposit formation in the aging eye.Proc Natl Acad Sci USA2015;112:1565-70

[93] Landis WJ,Weiner S.Topographic imaging of mineral and collagen in the calcifying turkey tendon.Connect Tissue Res1991;25:181-96

[94] Siegal DS,Newman JS,Hochman MG.Calcific tendinitis: a pictorial review.Can Assoc Radiol J2009;60:263-72

[95] Reynolds JL,McNair R.Multifunctional roles for serum protein fetuin-a in inhibition of human vascular smooth muscle cell calcification.J Am Soc Nephrol2005;16:2920-30

[96] de Faria LL, Babler F, Ferreira LC, de Noronha Junior OA, Marsolla FL, Ferreira DL. Soft tissue calcifications: a pictorial essay.Radiol Bras2020;53:337-44 PMCID:PMC7545731

[97] Wang D,Huang L.Unraveling an innate mechanism of pathological mineralization-regulated inflammation by a nanobiomimetic system.Adv Healthc Mater2021;10:e2101586

[98] Giachelli CM.Vascular calcification mechanisms.J Am Soc Nephrol2004;15:2959-64

[99] Schrijvers DM,Kockx MM,Martinet W.Phagocytosis of apoptotic cells by macrophages is impaired in atherosclerosis.Arterioscler Thromb Vasc Biol2005;25:1256-61

[100] Shanahan CM.Inflammation ushers in calcification: a cycle of damage and protection?.Circulation2007;116:2782-5

[101] Pugliese G,Blasetti Fantauzzi C.The dark and bright side of atherosclerotic calcification.Atherosclerosis2015;238:220-30

[102] Słojewski M,Safranow K.Microelements in stones, urine, and hair of stone formers: a new key to the puzzle of lithogenesis?.Biol Trace Elem Res2010;137:301-16

[103] Bala Y,Boivin G.Bone mineralization: from tissue to crystal in normal and pathological contexts.Osteoporos Int2013;24:2153-66

[104] Roschger P,Fratzl P.Bone mineralization density distribution in health and disease.Bone2008;42:456-66

[105] Roschger P,Paschalis E,Klaushofer K.Changes in the degree of mineralization with osteoporosis and its treatment.Curr Osteoporos Rep2014;12:338-50

[106] Kurdi MS.Chronic fluorosis: the disease and its anaesthetic implications.Indian J Anaesth2016;60:157-62 PMCID:PMC4800930

[107] Rodan GA.Therapeutic approaches to bone diseases.Science2000;289:1508-14

[108] Faibish D,Boskey AL.Mineral changes in osteoporosis: a review.Clin Orthop Relat Res2006;443:28-38 PMCID:PMC1459416

[109] Feroz S.7-fluoride-substituted hydroxyapatite. In: Khan AS, Chaudhry AA, editor. Handbook of ionic substituted hydroxyapatites, Soston, UK: Woodhead, 2020; pp. 175-96.

[110] Poole KE.Osteoporosis and its management.BMJ2006;333:1251-6 PMCID:PMC1702459

[111] Tamimi I,Sánchez-Siles JM.Composition and characteristics of trabecular bone in osteoporosis and osteoarthritis.Bone2020;140:115558

[112] Nobakhti S.On the relation of bone mineral density and the elastic modulus in healthy and pathologic bone.Curr Osteoporos Rep2018;16:404-10

[113] Shah FA.The many facets of micropetrosis - magnesium whitlockite deposition in bisphosphonate-exposed human alveolar bone with osteolytic metastasis.Micron2023;168:103441

[114] Shah FA.Magnesium whitlockite - omnipresent in pathological mineralisation of soft tissues but not a significant inorganic constituent of bone.Acta Biomater2021;125:72-82

[115] Meyer F,Kornak U.Chondrocytes from osteoarthritic and chondrocalcinosis cartilage represent different phenotypes.Front Cell Dev Biol2021;9:622287 PMCID:PMC8107373

[116] Fuerst M,Lammers L.Calcification of articular cartilage in human osteoarthritis.Arthritis Rheum2009;60:2694-703

[117] Derfus BA,Butler JJ.The high prevalence of pathologic calcium crystals in pre-operative knees.J Rheumatol2002;29:570-4

[118] Halverson PB.Patterns of radiographic abnormalities associated with basic calcium phosphate and calcium pyrophosphate dihydrate crystal deposition in the knee.Ann Rheum Dis1986;45:603-5 PMCID:PMC1001944

[119] Nalbant S,Kitumnuaypong T,Sieck M.Synovial fluid features and their relations to osteoarthritis severity: new findings from sequential studies.Osteoarthr Cartil2003;11:50-4Available from: https://www.sciencedirect.com/science/article/pii/S1063458402908617 [Last accessed on 5 July 2023].

[120] Rosenthal AK,Gohr CM.Characterization of articular calcium-containing crystals by synchrotron FTIR.Osteoarthr Cartil2008;16:1395-402 PMCID:PMC2574906

[121] Yan JF,Xiao BC.Pathological calcification in osteoarthritis: an outcome or a disease initiator?.Biol Rev Camb Philos Soc2020;95:960-85

[122] Rosenthal AK.Articular cartilage vesicles and calcium crystal deposition diseases.Curr Opin Rheumatol2016;28:127-32 PMCID:PMC6240443

[123] Scotchford CA,Ali SY.The isolation and characterization of magnesium whitlockite crystals from human articular cartilage.Osteoarthr Cartil1995;3:79-94

[124] Lee RS,Ali SY.Calcium phosphate microcrystal deposition in the human intervertebral disc.J Anat2006;208:13-9 PMCID:PMC2100183

[125] Hayes CW.Calcium hydroxyapatite deposition disease.Radiographics1990;10:1031-48

[126] Uhthoff HK.Calcific tendinopathy of the rotator cuff: pathogenesis, diagnosis, and management.J Am Acad Orthop Surg1997;5:183-91

[127] Landis WJ.A study of calcification in the leg tendons from the domestic turkey.J Ultrastruct Mol Struct Res1986;94:217-38

[128] Oliva F,Maffulli N.Physiopathology of intratendinous calcific deposition.BMC Med2012;10:95 PMCID:PMC3482552

[129] McCarty DJ Jr.Recurrent acute inflammation associated with focal apatite crystal deposition.Arthritis Rheum1966;9:804-19

[130] Gärtner J.Analysis of calcific deposits in calcifying tendinitis.Clin Orthop Relat Res1990;254:111-20

[131] Riley GP,Constant CR,Hazleman BL.Prevalence and possible pathological significance of calcium phosphate salt accumulation in tendon matrix degeneration.Ann Rheum Dis1996;55:109-15 PMCID:PMC1010104

[132] Penel G,Rey C.MicroRaman spectral study of the PO₄ and CO₃ vibrational modes in synthetic and biological apatites.Calcif Tissue Int1998;63:475-81

[133] Barron MJ,Mackie I.Hereditary dentine disorders: dentinogenesis imperfecta and dentine dysplasia.Orphanet J Rare Dis2008;3:31 PMCID:PMC2600777

[134] Jin Y.Supragingival calculus: formation and control.Crit Rev Oral Biol Med2002;13:426-41

[135] White DJ.Dental calculus: recent insights into occurrence, formation, prevention, removal and oral health effects of supragingival and subgingival deposits.Eur J Oral Sci1997;105:508-22

[136] Sakae T,Hirai G.Mode of occurrence of brushite and whitlockite in a sialolith.J Dent Res1981;60:842-4

[137] Anneroth G,Isacsson G.Crystalline structure of salivary calculi. a microradiographic and microdiffractometric study.J Oral Pathol1975;4:266-72

[138] Burnstein LS,Tannenbaum PJ,Mandel ID.The crystal chemistry of submandibular and parotid salivary gland stones.J Oral Pathol1979;8:284-91

[139] Boskey AL,Mandel ID.Phospholipids associated with human parotid gland sialoliths.Arch Oral Biol1983;28:655-7

[140] Nicoll R.The predictive value of arterial and valvular calcification for mortality and cardiovascular events.Int J Cardiol Heart Vessel2014;3:1-5 PMCID:PMC5801264

[141] Higgins CL,Morrisett JD.Quantification of calcification in atherosclerotic lesions.Arterioscler Thromb Vasc Biol2005;25:1567-76

[142] Reid JD.Medial calcification (whitlockite) in the aorta.Atherosclerosis1993;101:213-24

[143] Sage AP,Demer LL.Regulatory mechanisms in vascular calcification.Nat Rev Cardiol2010;7:528-36 PMCID:PMC3014092

[144] You AYF,St-Pierre JP.Raman spectroscopy imaging reveals interplay between atherosclerosis and medial calcification in the human aorta.Sci Adv2017;3:e1701156 PMCID:PMC5721727

[145] Chow B.The relationship between arterial stiffness and heart failure with preserved ejection fraction: a systemic meta-analysis.Heart Fail Rev2015;20:291-303

[146] Barasch E,Marino Larsen EK,Newman AB.Cardiovascular morbidity and mortality in community-dwelling elderly individuals with calcification of the fibrous skeleton of the base of the heart and aortosclerosis (The Cardiovascular Health Study).Am J Cardiol2006;97:1281-6

[147] Aikawa E,Figueiredo JL.Osteogenesis associates with inflammation in early-stage atherosclerosis evaluated by molecular imaging in vivo.Circulation2007;116:2841-50

[148] Wick G.Inflammation and atherosclerosis. Boston: Springer Science & Business Media; 2011.

[149] Saita A,Motta M.Stone composition: where do we stand?.Urol Int2007;79 Suppl 1:16-9

[150] Evan AP,Rittling SR.Apatite plaque particles in inner medulla of kidneys of calcium oxalate stone formers: osteopontin localization.Kidney Int2005;68:145-54

[151] He JY,Ouyang JM.Morphology, particle size distribution, aggregation, and crystal phase of nanocrystallites in the urine of healthy persons and lithogenic patients.IEEE Trans Nanobiosci2010;9:156-63

[152] Alelign T.Kidney stone disease: an update on current concepts.Adv Urol2018;2018:3068365 PMCID:PMC5817324

[153] Chaudhary A,Tandon C.In vitro evaluation of terminalia arjuna on calcium phosphate and calcium oxalate crystallization.Indian J Pharm Sci2010;72:340-5 PMCID:PMC3003167

[154] Bensatal A.Inhibition of crystallization of calcium oxalate by the extraction of Tamarix gallica L.Urol Res2008;36:283-7

[155] Griffith DP.Struvite stones.Kidney Int1978;13:372-82

[156] Luigia M.A review of pathological biomineral analysis techniques and classification schemes. In: Aydinalp C, editor. An introduction to the study of mineralogy. London: InTech; 2012.

[157] Coe FL,Worcester E.Kidney stone disease.J Clin Invest2005;115:2598-608

[158] Aggarwal KP,Kakkar M.Nephrolithiasis: molecular mechanism of renal stone formation and the critical role played by modulators.Biomed Res Int2013;2013:292953 PMCID:PMC3787572

[159] Coe FL,Asplin JR.The pathogenesis and treatment of kidney stones.N Engl J Med1992;327:1141-52

[160] Fleisch H.Inhibitors and promoters of stone formation.Kidney Int1978;13:361-71

[161] Ebrahimpour A,Nancollas GH.Induced crystal growth of calcium oxalate monohydrate at hydroxyapatite surfaces. the influence of human serum albumin, citrate, and magnesium.Langmuir1991;7:577-83

[162] Asplin JR,Parks JH,Hoyer JR.Contribution of human uropontin to inhibition of calcium oxalate crystallization.Kidney Int1998;53:194-9

[163] Stapleton A.Blood coagulation proteins and urolithiasis are linked: crystal matrix protein is the Fl activation peptide of human prothrombin.Br J Urol1995;75:712-9

[164] Pillay SN,Coe FL.Evidence that calgranulin is produced by kidney cells and is an inhibitor of calcium oxalate crystallization.Am J Physiol1998;275:F255-61

[165] Loeb JA,Huq M.Brain calcifications induce neurological dysfunction that can be reversed by a bone drug.J Neurol Sci2006;243:77-81

[166] Smeyers-Verbeke J,Pelsmaeckers J.The chemical composition of idiopathic nonarteriosclerotic cerebral calcifications.Neurology1975;25:48-57

[167] Oliveira JR.Primary brain calcification in patients undergoing treatment with the biphosphanate alendronate.Sci Rep2016;6:22961 PMCID:PMC4792151

[168] Lemos RR,Keasey MP.Chapter Fourteen - an update on primary familial brain calcification. In: Bhatia KP, Schneider SA, editors. International review of neurobiology. Cambridge: Academic Press. 2013; pp. 349-71.

[169] Jankovic J.Searching for a relationship between manganese and welding and Parkinson’s disease.Neurology2005;64:2021-8

[170] Bekiesinska-Figatowska M,Jurkiewicz E.Basal ganglia lesions in children and adults.Eur J Radiol2013;82:837-49

[171] Simoni M,Pracucci G.Prevalence of CT-detected cerebral abnormalities in an elderly Swedish population sample.Acta Neurol Scand2008;118:260-7

[172] Yamada M,Okamoto K.High frequency of calcification in basal ganglia on brain computed tomography images in Japanese older adults.Geriatr Gerontol Int2013;13:706-10

[173] Deng H,Jankovic J.Genetics and molecular biology of brain calcification.Ageing Res Rev2015;22:20-38

[174] Anderson SB,Hofmann-Rummelt C.Corneal calcification after amniotic membrane transplantation.Br J Ophthalmol2003;87:587-91 PMCID:PMC1771653

[175] Nicholson BP,Emch TM.Idiopathic dural optic nerve sheath calcification.Br J Ophthalmol2011;95:290, 299

[176] Russell SR,Schneider BL.Location, substructure, and composition of basal laminar drusen compared with drusen associated with aging and age-related macular degeneration.Am J Ophthalmol2000;129:205-14

[177] Hageman GS,Johnson LV.A common haplotype in the complement regulatory gene factor H (HF1/CFH) predisposes individuals to age-related macular degeneration.Proc Natl Acad Sci USA2005;102:7227-32

[178] Castellanos MR,El-Sayegh S,Buchbinder S.Breast cancer screening in women with chronic kidney disease: the unrecognized effects of metastatic soft-tissue calcification.Nat Clin Pract Nephrol2008;4:337-41

[179] Yildiz S,Aydin S.The association of breast arterial calcification and metabolic syndrome.Clinics2014;69:841-6 PMCID:PMC4286665

[180] Scimeca M,Antonacci C,Spagnoli LG.Microcalcifications in breast cancer: an active phenomenon mediated by epithelial cells with mesenchymal characteristics.BMC Cancer2014;14:286 PMCID:PMC4021315

[181] Scimeca M,Colombo D,Buonomo OC.Emerging prognostic markers related to mesenchymal characteristics of poorly differentiated breast cancers.Tumour Biol2016;37:5427-35

[182] Hassler O.Microradiographic investigations of calcifications of the female breast.Cancer1969;23:1103-9

[183] Scott R,Kendall C,Rogers K.Relationships between pathology and crystal structure in breast calcifications: an in situ X-ray diffraction study in histological sections.NPJ Breast Cancer2016;2:16029 PMCID:PMC5515336

[184] Kunitake JAMR,Nguyen KX.Correlative imaging reveals physiochemical heterogeneity of microcalcifications in human breast carcinomas.J Struct Biol2018;202:25-34 PMCID:PMC5835408

[185] Lakhdar A, Daudon M, Mathieu M, Kellum A, Balleyguier C, Bazin D. Underlining the complexity of the structural and chemical characteristics of ectopic calcifications in breast tissues through FE-SEM and μFTIR spectroscopy.Comptes Rendus Chimie2016;19:1610-24

[186] Haka AS,Fitzmaurice M,Dasari RR.Identifying microcalcifications in benign and malignant breast lesions by probing differences in their chemical composition using Raman spectroscopy.Cancer Res2002;62:5375-80

[187] Scott R,Stone N.Elemental vs. phase composition of breast calcifications.Sci Rep2017;7:136 PMCID:PMC5427875

[188] Tandan M,Reddy DN.Management of pancreatic calculi: an update.Gut Liver2016;10:873-80 PMCID:PMC5087925

[189] Narasimhulu KV,Rao JL.Structural studies of the biomineralized species of calcified pancreatic stones in patients suffering from chronic pancreatitis. Biophys Chem 2005;114:137-47.

[190] Pitchumoni CS,Gee Varghese PJ.Ultrastructure and elemental composition of human pancreatic calculi.Pancreas1987;2:152-8

[191] Klimas R,Gardner WA Jr.Prostatic calculi: a review.Prostate1985;7:91-6

[192] Sutor DJ.The crystalline composition of prostatic calculi.Br J Urol1974;46:533-5

[193] Hyun JS.Clinical significance of prostatic calculi: a review.World J Mens Health2018;36:15-21 PMCID:PMC5756803

[194] Wallingford MC,Chavkin NW,Frasch MG.Placental vascular calcification and cardiovascular health: it is time to determine how much of maternal and offspring health is written in stone.Front Physiol2018;9:1044 PMCID:PMC6090024

[195] Poggi SH,Demer LL,Koos BJ.Placental calcification: a metastatic process?.Placenta2001;22:591-6

[196] Chen KH,Lee YH.Exploring the relationship between preterm placental calcification and adverse maternal and fetal outcome.Ultrasound Obstet Gynecol2011;37:328-34

[197] Marchiori E,Zanetti G.Lymph node calcifications.J Bras Pneumol2018;44:83 PMCID:PMC6044648

[198] Sakae T.Crystals and calcification patterns in two lymph node calcifications.J Oral Pathol1987;16:456-62

[199] Kim MH,Kim NN,Ahn SH.A rotational ablation tool for calcified atherosclerotic plaque removal.Biomed Microdevices2011;13:963-71

[200] Kaul A,Bapatla A.Current treatment modalities for calcified coronary artery disease: a review article comparing novel intravascular lithotripsy and traditional rotational atherectomy.Cureus2020;12:e10922 PMCID:PMC7657441

[201] Jahnen-Dechent W,Ketteler M.Mineral chaperones: a role for fetuin-A and osteopontin in the inhibition and regression of pathologic calcification.J Mol Med2008;86:379-89

[202] Schibler D,Fleisch H.Inhibition by pyrophosphate and polyphosphate of aortic calcification induced by vitamin D3 in rats.Clin Sci1968;35:363-72.

[203] O’Neill WC,Malluche HH,Riser BL.Treatment with pyrophosphate inhibits uremic vascular calcification.Kidney Int2011;79:512-7 PMCID:PMC3183997

[204] Wu M,Giachelli CM.Vascular calcification: an update on mechanisms and challenges in treatment.Calcif Tissue Int2013;93:365-73 PMCID:PMC3714357

[205] Schinke T,Trindl A,Müller-Esterl W.The serum protein α₂-HS glycoprotein/fetuin inhibits apatite formation in vitro and in mineralizing calvaria cells.J Biol Chem1996;271:20789-96

[206] Heiss A,Endo H.Structural dynamics of a colloidal protein-mineral complex bestowing on calcium phosphate a high solubility in biological fluids.Biointerphases2007;2:16-20

[207] Heiss A,Denecke B.Structural basis of calcification inhibition by α₂-HS glycoprotein/fetuin-A.J Biol Chem2003;278:13333-41

[208] Jahnen-Dechent W,Schäfer C.Fetuin-A regulation of calcified matrix metabolism.Circ Res2011;108:1494-509

[209] Zebboudj AF,Boström K.Matrix GLA protein, a regulatory protein for bone morphogenetic protein-2.J Biol Chem2002;277:4388-94

[210] Hruska KA,Saab G.Bone morphogenetic proteins in vascular calcification.Circ Res2005;97:105-14

[211] Mckee M.Osteopontin at mineralized tissue interfaces in bone, teeth, and osseointegrated implants: Ultrastructural distribution and implications for mineralized tissue formation, turnover, and repair.Microsc Res Tech1996;33:141-64

[212] McKee MD.Osteopontin: an interfacial extracellular matrix protein in mineralized tissues.Connect Tissue Res1996;35:197-205

[213] Oikonomaki T,Ntrinias T.The effect of vitamin K2 supplementation on vascular calcification in haemodialysis patients: a 1-year follow-up randomized trial.Int Urol Nephrol2019;51:2037-44

[214] Eastell R,Watts NB.Bisphosphonates for postmenopausal osteoporosis.Bone2011;49:82-8

[215] Francis MD,Fleisch H.Diphosphonates inhibit formation of calcium phosphate crystals in vitro and pathological calcification in vivo.Science1969;165:1264-6

[216] van der Sluis IM, Boot AM, Vernooij M, Meradji M, Kroon AA. Idiopathic infantile arterial calcification: clinical presentation, therapy and long-term follow-up.Eur J Pediatr2006;165:590-3

[217] Persy V,Ketteler M.Bisphosphonates prevent experimental vascular calcification: treat the bone to cure the vessels?.Kidney Int2006;70:1537-8

[218] Shiraishi N,Miyoshi T.Successful treatment of a patient with severe calcific uremic arteriolopathy (calciphylaxis) by etidronate disodium.Am J Kidney Dis2006;48:151-4

[219] Jansen RS,Mahakena S.ABCC6-mediated ATP secretion by the liver is the main source of the mineralization inhibitor inorganic pyrophosphate in the systemic circulation-brief report.Arterioscler Thromb Vasc Biol2014;34:1985-9 PMCID:PMC6743317

[220] Li Q,Pinkerton AB.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.J Invest Dermatol2019;139:360-8 PMCID:PMC6342656

[221] Pomozi V,van de Wetering K.Pyrophosphate supplementation prevents chronic and acute calcification in ABCC6-deficient mice.Am J Pathol2017;187:1258-72 PMCID:PMC5455066

[222] Zhao J,Sundberg JP,Li Q.Plasma PPi deficiency is the major, but not the exclusive, cause of ectopic mineralization in an Abcc6(-/-) mouse model of PXE.J Invest Dermatol2017;137:2336-43 PMCID:PMC7069658

[223] Garti N,Sarig S.The inhibitory effect of polymeric carboxylic amino-acids and urine on calcium oxalate crystallization.Biochem Biophys Res Commun1980;97:1154-62

[224] Kleinman JG,Beshensky AM.Acidic polyanion poly(acrylic acid) prevents calcium oxalate crystal deposition.Kidney Int2008;74:919-24 PMCID:PMC2566899

[225] Worcester EM,Beshensky AM.The calcium oxalate crystal growth inhibitor protein produced by mouse kidney cortical cells in culture is osteopontin.J Bone Miner Res1992;7:1029-36

[226] Wesson JA,Mazzali M.Osteopontin is a critical inhibitor of calcium oxalate crystal formation and retention in renal tubules.J Am Soc Nephrol2003;14:139-47

[227] Cohen GF.Sodium thiosulfate in the treatment of calciphylaxis.J Clin Aesthet Dermatol2013;6:41-4 PMCID:PMC3662683

[228] Guerra G,Ross EA.Rapid resolution of calciphylaxis with intravenous sodium thiosulfate and continuous venovenous haemofiltration using low calcium replacement fluid: case report.Nephrol Dial Transplant2005;20:1260-2

[229] Cicone JS,Embert CD.Successful treatment of calciphylaxis with intravenous sodium thiosulfate.Am J Kidney Dis2004;43:1104-8

[230] Yatzidis H.Successful sodium thiosulphate treatment for recurrent calcium urolithiasis.Clin Nephrol1985;23:63-7

[231] Sun XY,Ouyang JM.Effect of crystal shape and aggregation of calcium oxalate monohydrate on cellular toxicity in renal epithelial cells.ACS Omega2017;2:6039-52 PMCID:PMC6044778

[232] Bazin D,Matzen G,Daudon M.Heavy elements in urinary stones.Urol Res2007;35:179-84

[233] Meyer J.The role of trace metals in calcium urolithiasis.Invest Urol1977;14:347-50

[234] Muñoz JA.Effects of trace metals on the inhibition of calcium oxalate crystallization.Urol Res2005;33:267-72

[235] Atakan IH,Seren G,Gül H.Serum, urinary and stone zinc, iron, magnesium and copper levels in idiopathic calcium oxalate stone patients.Int Urol Nephrol2007;39:351-6

[236] Levy RJ,Flowers WB.Initiation of mineralization in bioprosthetic heart valves: studies of alkaline phosphatase activity and its inhibition by AlCl₃ or FeCl₃ preincubations.J Biomed Mater Res1991;25:905-35

[237] Ali SY.Apatite-type crystal deposition in arthritic cartilage.Scan Electron Microsc1985;Pt 4:1555-66

[238] Usai D,Dal Sasso G.Late pleistocene/early holocene evidence of prostatic stones at Al khiday cemetery, central sudan.PLoS One2017;12:e0169524 PMCID:PMC5266250