Heparan sulfate modification in dentinogenesis

The formation of dentin is a dynamic process that is triggered and controlled by a functional network of matrix molecules and diffusible growth factors. Heparan sulfate (HS) is ubiquitously present on the cell surface and in the extracellular matrix, and it is an essential regulator of cell signaling and development. The specific sulfation patterns of HS determine the specificity and affinity of ligand binding, and distinct HS sulfation patterns in different tissues during different developmental stages participate in the regulation of cellular signaling. The present brief review describes the significance of the sulfation of cell surface HS in dentinogenesis. In odontoblast differentiation, 6-O-desulfation of extracellular HS proteoglycans is an important post-synthetic modification that is critical for the activation of Wnt signaling in odontoblasts and the subsequent production of dentin matrix. The endosulfatases Sulf1 and Sulf2 catalyze HS 6-O-desulfation on the surface of odontoblast cells. This post-synthetic modification of HS sulfation affects the binding affinity of HS for Wnt10a and subsequently modulates canonical Wnt signaling to induce dentin sialophosphoprotein (DSPP) mRNA expression.