Extracellular matrix protein DMP1 suppresses osteogenic differentiation of Mesenchymal Stem Cells

Mesenchymal Stem Cells (MSCs) are self-renewing and multipotent stem cells which was investigated for diverse clinical applications. However, complex mechanism of MSC5 fate determination is still not fully disclosed. Extracellular matrix (ECM) proteins contribute to maintain MSCs sternness by providing extracellular microenvironment. Increasing evidences show that ECM proteins could also regulate the fate of MSCs directly. Dentin matrix protein 1 (DMP1) is an ECM protein enrich in bone tissue and terminal cells, which well-known in promoting osteoblasts and osteocytes maturation, and facilitate mineralization. Recently, our experiment indicated that DMPI was also expressed in MSCs of long bone. In present study, it is found that DMPI expressed in Prx1 positive MSCs. And, DMP1 is down-regulated in early osteoblasts and up-regulated again in mature osteoblasts. DMP1 conditional knockout mice model under Prxlcre was generated to explore whether DMP1 regulates MSCs osteogenic differentiation. Specific ablation of DMPI in Prx1 positive MSC5 increased bone mass in vivo and promoted osteoblasts activity in vitro. This study provides a new understanding of DMP1 's function in regulation of osteogenesis: not only an enhancer of bone formation, but also a negative regulator of MSCs differentiation in bone. (C) 2018 Elsevier Inc. All rights reserved.