Primary Structure and Phosphorylation of Dentin Matrix Protein 1 (DMP1) and Dentin Phosphophoryn (DPP) Uniquely Determine Their Role in Biomineralization.

TLDR

SIBLING proteins are the major noncollagenous, highly acidic and phosphorylated components of bone and dentin, essential for forming collagenous mineralized tissues. The study aimed to determine whether different SIBLINGs regulate biomineralization similarly and how phosphorylation influences their activity. The authors examined the effects of dentin matrix protein 1 and dentin phosphophoryn on mineral morphology and organization in vitro. The results showed that phosphorylation profoundly alters the distinct roles of DMP1 and DPP, with phosphorylated forms promoting organized mineralization of collagen fibrils and, for DMP1, forming mineral bundles even without collagen, indicating that primary structure and phosphorylation uniquely dictate SIBLING function.

Abstract

The SIBLING (small integrin-binding ligand N-linked glycoproteins) family is the major group of noncollagenous proteins in bone and dentin. These extremely acidic and highly phosphorylated extracellular proteins play critical roles in the formation of collagenous mineralized tissues. Whereas the lack of individual SIBLINGs causes significant mineralization defects in vivo, none of them led to a complete cessation of mineralization suggesting that these proteins have overlapping functions. To assess whether different SIBLINGs regulate biomineralization in a similar manner and how phosphorylation impacts their activity, we studied the effects of two SIBLINGs, dentin matrix protein 1 (DMP1) and dentin phosphophoryn (DPP), on mineral morphology and organization in vitro. Our results demonstrate distinct differences in the effects of these proteins on mineralization. We show that phosphorylation has a profound effect on the regulation of mineralization by both proteins. Specifically, both phosphorylated proteins facilitated organized mineralization of collagen fibrils and phosphorylated DMP1-induced formation of organized mineral bundles in the absence of collagen. In summary, these results indicate that the primary structure and phosphorylation uniquely determine functions of individual SIBLINGs in regulation of mineral morphology and organization.