Cell Surface Accumulation of Intracellular Leucine Proline-Enriched Proteoglycan 1 Enhances Odontogenic Potential of Human Dental Pulp Stem Cells.

Abstract

Primary dental pulp cells can be differentiated into odontoblast-like cells, which are responsible for dentin formation and mineralization. Successful differentiation of primary dental pulp cells can be verified using a few markers. However, odontoblast-specific cell surface markers have not been fully studied yet. LEucine PRoline-Enriched Proteoglycan 1 (LEPRE1) is a basement membrane-associated proteoglycan. LEPRE1 protein levels are increased during odontoblastic differentiation of human dental pulp cells (hDPCs). Intracellular and cell surface accumulation of this protein completely disappeared during dentin maturation and mineralization. Cell surface binding of an anti-LEPRE1 monoclonal antibody that could recognize an extracellular region was gradually increased in the odontoblastic stage. Overexpression and knockdown experiments showed that accumulation of intracellular LEPRE1 could lead to inefficient odontoblastic differentiation and that the movement of LEPRE1 from intracellular region to the cell surface was required for odontoblastic differentiation. Indeed, when LEPRE1 already located on the cell surface was blocked by the anti-LEPRE1 monoclonal antibody, odontoblastic differentiation of hDPCs was inhibited. In this study, we looked at other aspects of LEPRE1 function as a cell surface molecule rather than its known intracellular hydroxylase activity. Our results indicate that this protein has potential as a specific cell surface marker in odontoblastic differentiation.