骨髓基质干细胞（MSC）具有自我更新、分化为成骨细胞并促进骨再生的重要功能，然而关于MSC的干性维持和分化的调控机理还有问题尚待解决。近期研究证明雌激素相关受体（ERR）家族对干细胞的干性维持及分化具有重要作用。为揭示ERRa对MSC的调控机理，本项目将从以下方面探索研究：1）利用ERRα的激动剂和拮抗剂，探索ERRα与MSC干性维持关键因子的相互调控作用；以及研究ERRa对MSC分化能力的影响调节；2）通过ERRa对MSC线粒体能量输出、活性氧产生及下游通路的调节，研究其对MSC的干性维持和分化的影响；3）利用条件性基因敲除小鼠，在成骨前体细胞特异性敲除ERRa进一步验证ERRa在体内对MSC成骨分化能力的影响。本研究将从核受体ERRa的分子调控水平，探讨MSC干性维持的调控机理以及分化方向的决定，对研究衰老过程中出现的MSC功能衰退以及数量的减少具有重要意义。

Bone marrow derived mesenchymal stem cell (MSC) has self-renewal, multipotent differentiation capability, and has been confirmed to be responsible for bone regeneration. However, the underlying mechanisms of MSC stemness maintenance and differentiation have not been solved. Previous studies have reported that estrogen-related receptor(ERR) family is involved in stem cell self-renewal and differentiation. This current proposal will focused on 1) using ERRa agonist/antagonist, investigate the regulation mechanism between ERRa and other regulators of pluripotency; investigate the role of ERRa in MSC differentiation; 2) identify ERRa as a major actor in the regulation of energy metabolism in MSC; investigate its role in regulation of ROS , downstream signal pathway, and crosstalk with MSC pluripotency and differentiation ;3) using conditional knockout mice , silence ERRa in osteoblastic lineage cell to investigate the role of ERRa in osteoblastic differentiation and bone formation in vivo. This proposal will contribute to discover the molecular mechanism of MSC stemness maintenance and differentiation, find new target for bone regeneration and repair, and significantly contribute to study in MSC decreased number and quality of cell with aging.