Spondin-1 Inhibits Odontoblastic Differentiation of Human Dental Pulp Stem Cells

Reparative dentin formation is a defensive response that restores a mineralized barrier to protect the dental pulp following various stimuli, such as bacterial invasion, tooth preparation, or restorative materials. However, reparative dentin is limited, and to avoid pathological calcification or pulp canal obliteration, mineral deposition must be restricted to the injured area and temporally restrained once the barrier is reestablished. This suggests the existence of negative regulators that can halt odontoblastic differentiation; however, such inhibitory regulators remain incompletely defined. Spondin-1 (SPON1) is an extracellular matrix protein known to regulate bone homeostasis and act as a negative regulator of bone mass; however, the effects of SPON1 on odontoblastic differentiation of dental pulp stem cells (DPSCs) remain unclear. This study aimed to analyze the effects of SPON1 on odontoblastic differentiation of human DPSCs (HDPSCs). SPON1 was expressed in the odontoblastic layer and dental pulp tissue, and its expression was significantly decreased at the beginning of reparative dentin formation in rats. Treatment with SPON1 inhibited odontoblastic differentiation of HDPSCs by blocking the expression of non-phosphorylated β-catenin, while neutralizing SPON1 significantly enhanced odontoblastic differentiation of HDPSCs. These findings suggest that SPON1 functions as a negative regulator of odontoblastic differentiation during reparative dentin formation.