Extracellular matrix protein DMP1 suppresses osteogenic differentiation of Mesenchymal Stem Cells
Extracellular matrix protein DMP1 suppresses osteogenic differentiation of Mesenchymal Stem Cells
复制标题
细胞外基质蛋白DMP1抑制间充质干细胞的成骨分化
DOI：
10.1016/j.bbrc.2018.05.092
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发表时间：
2018
影响因子：
3.1
通讯作者：
Sun Yao
中科院分区：
文献类型：
--
作者：
Zhang Shufan;Wan Huixuan;Wang Peng;Liu Mengmeng;Li Gongchen;Zhang Chunxue;Sun Yao
间充质干细胞(MSCs)是一种具有自我更新功能的多潜能干细胞，临床应用广泛。然而，决定MSCs命运的复杂机制仍未完全揭示。细胞外基质(ECM)蛋白通过提供细胞外微环境来维持MSCs的干性。越来越多的证据表明，ECM蛋白也可以直接调控MSCs的命运。牙本质基质蛋白1(DMP1)是一种丰富于骨组织和终末细胞的细胞外基质蛋白，具有促进成骨细胞和骨细胞成熟、促进矿化的作用。最近，我们的实验表明，DMP1在长骨的MSCs中也有表达。本研究发现在PRX1阳性的MSCs中有DMP1的表达。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。建立Prx1cre下DMP1条件性基因敲除小鼠模型，探讨DMP1对MSCs成骨分化的调控作用。特异性去除PRX1阳性MSCs中的DMP1可增加成骨细胞活性，提高成骨细胞活性。本研究对DMP1在成骨调控中的S功能提供了新的认识：既是骨形成的促进剂，又是骨髓间充质干细胞在骨中分化的负调控因子。
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 massin vivoand promoted osteoblasts activityin 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.