Department of Oral Implantology, School of Stomatology, Tongji University, Shanghai Engineering Research Center of Tooth Restoration and Regeneration, Shanghai, 200072, China.
Tongji University School of Medicine, Stem Cell Translational Research Center, Tongji Hospital, Shanghai, 200065, China.
Biochem Biophys Res Commun. 2018 Jul 2;501(4):968-973. doi: 10.1016/j.bbrc.2018.05.092. Epub 2018 May 19.
Mesenchymal Stem Cells (MSCs) are self-renewing and multipotent stem cells which was investigated for diverse clinical applications. However, complex mechanism of MSCs fate determination is still not fully disclosed. Extracellular matrix (ECM) proteins contribute to maintain MSCs stemness 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 DMP1 was also expressed in MSCs of long bone. In present study, it is found that DMP1 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 Prx1cre was generated to explore whether DMP1 regulates MSCs osteogenic differentiation. Specific ablation of DMP1 in Prx1 positive MSCs 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.
间充质干细胞（MSCs）是具有自我更新和多能性的干细胞，已经被广泛研究用于各种临床应用。然而，MSCs 命运决定的复杂机制尚未完全揭示。细胞外基质（ECM）蛋白通过提供细胞外微环境有助于维持 MSCs 的干性。越来越多的证据表明，ECM 蛋白也可以直接调节 MSCs 的命运。牙本质基质蛋白 1（DMP1）是一种富含骨组织和终末细胞的 ECM 蛋白，其功能是促进成骨细胞和破骨细胞的成熟，并促进矿化。最近，我们的实验表明 DMP1 也在长骨的 MSCs 中表达。在本研究中，我们发现 DMP1 在 Prx1 阳性的 MSCs 中表达。而且，DMP1 在早期成骨细胞中下调，在成熟成骨细胞中再次上调。生成了在 Prx1cre 下表达 DMP1 条件性敲除的小鼠模型，以探讨 DMP1 是否调节 MSCs 的成骨分化。Prx1 阳性 MSCs 中 DMP1 的特异性缺失增加了体内骨量，并促进了体外成骨细胞的活性。这项研究提供了对 DMP1 在调节成骨作用的新认识：它不仅是骨形成的增强剂，而且是骨中 MSCs 分化的负调节剂。
