软骨下骨作为骨性关节炎发病中的一个关键因素越来越受临床医生和学者们重视。异常应力作用下软骨下骨先发生微骨折，随后募集MSCs，启动骨重塑，长期异常修复后导致软骨下骨硬化等改变。可见OA发病早期，软骨下骨MSCs的生物学行为和功能的正常与否极为重要。研究发现软骨下骨TGF-beta信号参与了OA的发生，且TGF-beta信号对MSCs有多方位调控。结合前期研究结果，补肾活血方能很好逆转小鼠OA软骨下骨硬化表型，并能上调TGF-beta信号促进MSCs迁移分化。因此本项目拟借助最新的细胞谱系示踪技术，利用能特异性定位软骨下骨MSCs的转基因小鼠（Osterix-CreER），可视化体内示踪软骨下骨MSCs在OA进程中的迁移增殖分化和能量代谢情况；通过体内外联合探究TGF-beta信号通路参与该过程的具体机制；并探析补肾活血中药可能的调控机制，以更好的明确OA的发生机制和关键作用靶点。

The subchondral bone as another key factors in the pathogenesis of osteoarthritis (OA) is more and more important. Abnormal stress under the action of the subchondral bone which lead to micro fracture first, then raise mesenchymal stem cells and bone remodeling, sclerosis of subchondral bone after long-term abnormal repair change. Thus, the pathogenesis of early OA probably the subchondral bone MSCs abnormalities. The study found that the subchondral bone TGF - beta signal is likely to be involved in the occurrence of OA, and TGF - beta signal of MSCs have directional control. Combined with previous studies have found that BSHX can reverse well subchondral bone sclerosis phenotype in knee osteoarthritis, at the same time it can increase TGF - beta signal promote MSCs migration and differentiation. This project intends to adopt the subchondral bone MSCs specificity Osterix – CreER mice as the OA subchondral bone proliferation/differentiation/ migration tools, build a model of OA, tracking of MSCs in the process of OA subchondral bone, how to migration/proliferation/differentiation and how is the energy metabolism. From in vivo and in vitro to explore the mechanism of the TGF-beta signal regulate migration/proliferation/differentiation and energy metabolism of the subchondral bone MSCs. Besides, it shows how BSHX regulate TGF-beta signaling pathway to delay the progress of OA.