BMSCs来源的微囊泡通过S1P/S1P1信号通路激活线粒体融合进而通过GPS2调节组蛋白乙酰化促进软骨细胞修复的机制研究

目前针对软骨细胞损伤的修复方法不多，效果欠佳，且有限的方法中也并未阐明机制。线粒体是细胞进行氧化磷酸化并产生能量的重要细胞器，细胞的修复行为与线粒体的功能及其形态变化密切相关。课题组前期研究发现，骨髓基质干细胞来源的微囊泡可以通过S1P/S1P1信号通路促进软骨细胞的增殖修复。在此过程中，软骨细胞内线粒体数量和形态都发生了巨大变化。据此我们推测线粒体在软骨细胞修复过程中可能发挥了重要作用。本课题将紧扣上一课题的研究思路和结果，从微囊泡通过S1P/S1P1信号通路对软骨细胞增殖的影响，研究线粒体功能和形态变化与该影响之间的机制联系。同时从线粒体通过G蛋白通路抑制因子2(GPS2)对细胞核内组蛋白乙酰化的调节入手，研究微囊泡对软骨细胞线粒体的融合、生物合成调节的具体机制和途径。本研究不仅为微囊泡修复软骨细胞损伤提供理论依据，也将为线粒体与细胞核的信号交流途径提供新的证据。

At present, there are few effective methods for repairing chondrocyte injury, and the mechanism has not been elucidated in the methods. Mitochondria is an important organelle for oxidative phosphorylation and energy production. The repair of cells is closely related to the function and morphological changes of mitochondria. Our previous studies have found that bone marrow mesenchymal stem cellderived microcapsules can promote the proliferation and repair of chondrocytes via the S1P/S1P1 signaling pathway. In this process, there have been changed dramatically for the quantity and morphology of mitochondria in chondrocytes. Therefore, we speculate that mitochondria may play an important role in the process of repairing chondrocytes. In this project, we will study the effect of microvesicles on chondrocyte proliferation through S1P/S1P1 signaling pathway, and discuss the relationship between the functional and morphological changes of mitochondrial and this effect. At the same time, we will detect histone acetylation regulated by mitochondria through G protein pathway inhibitor 2 (GPS2), and elucidate the mechanism and pathway of chondrocyte mitochondrial fusion and biosynthesis regulated by microvesicles. This study will not only provide a theoretical basis for the repair of chondrocyte damage by microvesicles, but also provide a new evidence for the signaling pathway between mitochondria and nucleus.