Dentin matrix protein 1 and phosphate homeostasis are critical for postnatal pulp, dentin and enamel formation

Abstract

Dentin matrix protein 1 (DMP1) protects cells involved in tooth formation against regulated cell death caused by high blood phosphate (Pi). Elevated Pi levels, caused by disorders such as chronic kidney disease, cause abnormal tooth formation. Afsaneh Rangiani and her colleagues from the Baylor College of Dentistry, USA, used mutant mice to dissect the roles of DMP1 and Pi in controlling the formation of dental pulp, enamel and dentin—major components of teeth. DMP1-deficient mice with elevated Pi levels had severe defects in pulp formation and the deposition of enamel and dentin. These defects were correlated with the premature death of ameloblastas and odontoblasts, the cells that produce enamel and dentin, respectively. No defects in tooth formation were found in DMP1-deficient mice with normal Pi levels.

Keywords

apoptosis / dentin / dentin matrix protein 1 / enamel / Klotho / phosphate

References

[1] Fisher LW, Jain A, Tayback M. Small integrin binding ligand N-linked glycoprotein gene family expression in different cancers. Clin Cancer Res, 2004, 10(24): 8501-8511.

[2] Qin C, D’Souza R, Feng JQ. Dentin matrix protein 1 (DMP1): new and important roles for biomineralization and phosphate homeostasis. J Dent Res, 2007, 86(12): 1134-1141.

[3] Ye L, MacDougall M, Zhang S. Deletion of dentin matrix protein-1 leads to a partial failure of maturation of predentin into dentin, hypomineralization, and expanded cavities of pulp and root canal during postnatal tooth development. J Biol Chem, 2004, 279(18): 19141-19148.

[4] Lu Y, Ye L, Yu S. Rescue of odontogenesis in Dmp1-deficient mice by targeted re-expression of DMP1 reveals roles for DMP1 in early odontogenesis and dentin apposition in vivo. Dev Biol, 2007, 303(1): 191-201.

[5] Feng JQ, Ward LM, Liu S. Loss of DMP1 causes rickets and osteomalacia and identifies a role for osteocytes in mineral metabolism. Nat Genet, 2006, 38(11): 1310-1315.

[6] Lorenz-Depiereux B, Bastepe M, Benet-Pages A. DMP1 mutations in autosomal recessive hypophosphatemia implicate a bone matrix protein in the regulation of phosphate homeostasis. Nat Genet, 2006, 38(11): 1248-1250.

[7] Jiang B, Cao Z, Lu Y. DMP1 C-terminal mutant mice recapture the human ARHR tooth phenotype. J Bone Miner Res, 2010, 25(10): 2155-2164.

[8] Lu Y, Yuan B, Qin C. The biological function of DMP-1 in osteocyte maturation is mediated by its 57-kDa C-terminal fragment. J Bone Miner Res, 2011, 26(2): 331-340.

[9] Martin A, Quarles LD. Evidence for FGF23 involvement in a bone-kidney axis regulating bone mineralization and systemic phosphate and vitamin D homeostasis. Adv Exp Med Biol, 2012, 728: 65-83.

[10] Nakatani T, Sarraj B, Ohnishi M. In vivo genetic evidence for Klotho-dependent, fibroblast growth factor 23 (Fgf23)-mediated regulation of systemic phosphate homeostasis. FASEB J, 2009, 23(2): 433-441.

[11] Kurosu H, Ogawa Y, Miyoshi M. Regulation of fibroblast growth factor-23 signaling by Klotho. J Biol Chem, 2006, 281(10): 6120-6123.

[12] Li SA, Watanabe M, Yamada H. Immunohistochemical localization of Klotho protein in brain, kidney, and reproductive organs of mice. Cell Struct Funct, 2004, 29(4): 91-99.

[13] Urakawa I, Yamazaki Y, Shimada T. Klotho converts canonical FGF receptor into a specific receptor for FGF23. Nature, 2006, 444(7120): 770-774.

[14] Suzuki H, Amizuka N, Oda K. Involvement of the Klotho protein in dentin formation and mineralization. Anat Rec (Hoboken), 2008, 291(2): 183-190.

[15] Chu EY, Fong H, Blethen FA. Ablation of systemic phosphate-regulating gene fibroblast growth factor 23 (Fgf23) compromises the dentoalveolar complex. Anat Rec (Hoboken), 2010, 293(7): 1214-1226.

[16] Bai XY, Miao D, Goltzman D. The autosomal dominant hypophosphatemic rickets R176Q mutation in fibroblast growth factor 23 resists proteolytic cleavage and enhances in vivo biological potency. J Biol Chem, 2003, 278(11): 9843-9849.

[17] White KE, Carn G, Lorenz-Depiereux B. Autosomal-dominant hypophosphatemic rickets (ADHR) mutations stabilize FGF-23. Kidney Int, 2001, 60(6): 2079-2086.

[18] Martinez EF, da Silva LA, Furuse C. Dentin matrix protein 1 (DMP1) expression in developing human teeth. Braz Dent J, 2009, 20(5): 365-369.

[19] Rangiani A, Cao Z, Sun Y. Protective roles of DMP1 in high phosphate homeostasis. PLoS One, 2012, 7(8): e42329.

[20] Kuro-o M, Matsumura Y, Aizawa H. Mutation of the mouse Klotho gene leads to a syndrome resembling ageing. Nature, 1997, 390(6655): 45-51.

[21] Feng JQ, Huang H, Lu Y. The Dentin matrix protein 1 (Dmp1) is specifically expressed in mineralized, but not soft, tissues during development. J Dent Res, 2003, 82(10): 776-780.

[22] Tsujikawa H, Kurotaki Y, Fujimori T. Klotho, a gene related to a syndrome resembling human premature aging, functions in a negative regulatory circuit of vitamin D endocrine system. Mol Endocrinol, 2003, 17(12): 2393-2403.

[23] Brownstein CA, Zhang J, Stillman A. Increased bone volume and correction of HYP mouse hypophosphatemia in the Klotho/HYP mouse. Endocrinology, 2010, 151(2): 492-501.

[24] Ye L, Mishina Y, Chen D. Dmp1-deficient mice display severe defects in cartilage formation responsible for a chondrodysplasia-like phenotype. J Biol Chem, 2005, 280(7): 6197-6203.

[25] Ling Y, Rios HF, Myers ER. DMP1 depletion decreases bone mineralization in vivo: an FTIR imaging analysis. J Bone Miner Res, 2005, 20(12): 2169-2177.

[26] Liu H, Fergusson MM, Castilho RM. Augmented Wnt signaling in a mammalian model of accelerated aging. Science, 2007, 317(5839): 803-806.

[27] Lv K, Huang H, Lu Y. Circling behavior developed in Dmp1 null mice is due to bone defects in the vestibular apparatus. Int J Biol Sci, 2010, 6(6): 537-545.

[28] Kuro-o M. Klotho and aging. Biochim Biophys Acta, 2009, 1790(10): 1049-1058.

[29] Kuro-o M. Klotho as a regulator of fibroblast growth factor signaling and phosphate/calcium metabolism. Curr Opin Nephrol Hypertens, 2006, 15(4): 437-441.

[30] Narayanan K, Gajjeraman S, Ramachandran A. Dentin matrix protein 1 regulates dentin sialophosphoprotein gene transcription during early odontoblast differentiation. J Biol Chem, 2006, 281(28): 19064-19071.

[31] Yoshimura I, Suzuki S, Hayakawa M. Application of Cre-loxP system to the urinary tract and cancer gene therapy. Mol Urol, 2001, 5(2): 81-84.

[32] Naikmasur V, Guttal K, Bhargava P. Tumoral calcinosis with dental manifestations—a case report. Dent Update, 2008, 35(2): 134-136, 138.

[33] Suzuki H, Amizuka N, Oda K. Histological evidence of the altered distribution of osteocytes and bone matrix synthesis in Klotho-deficient mice. Arch Histol Cytol, 2005, 68(5): 371-381.