Role of SIBLINGs on matrix mineralization: Focus on dentin matrix protein 1 (DMP1)

Abstract

Dentin matrix protein 1 (DMP1) is a member of the SIBLING (Small Integrin-Binding Ligand, N-linked Glycoprotein) family of genetically related noncollagenous proteins in mineralized tissues. DMP1 was originally postulated to be dentin-specific, but its expression was later found to be present predominantly in osteocyte of bone. A unique feature of DMP1 is its unusually large number of acidic domains. Because of its highly acidic nature, DMP1 can bind to calcium, thereby regulating matrix mineralization. Protein chemistry analysis showed that full-length DMP1 is a precursor that is cleaved into NH2-terminal 37-kDa and COOH-terminal 57-kDa fragments. Functional analyses demonstrated that the COOH-terminal 57-kDa fragment of DMP1 is essential for mineralization and maturation of osteoblast to osteocyte. The phenotype of DMP1-null mice with hypophosphatemia led to the discovery of DMP1 mutations in autosomal-recessive hypophosphatemic rickets (ARHR). Both DMP1-null mice and individuals with ARHR exhibit elevated serum FGF23 that causes increased renal phosphate wasting, leading to hypophosphatemia. These findings indicate that regulation of matrix mineralization by DMP1 is coupled to renal phosphate homeostasis through FGF23 production by osteocyte. This review summarizes the current understanding of DMP1 focusing on bone formation and homeostasis.