骨骼干细胞的抗衰老与免疫抑制功能在关节软骨再生过程中的作用研究

骨关节炎是一种表现为关节软骨降解，局部炎症水平升高的退行性疾病。关节软骨表面的骨骼干细胞（SSCs）通过自我更新和分化，维持关节软骨的稳态与再生修复, 它还具有免疫抑制作用。但是SSCs随着衰老进程，或者炎症水平的升高，其修复软骨再生的能力下降。我们前期研究发现了转录因子Foxp1蛋白，通过抑制p16的表达，调控了SSCs的衰老和骨质疏松发生过程。在本项目中，我们期待深入研究SSCs细胞衰老与免疫抑制的调控机制。其中包括：利用遗传示踪技术，分析关节SSCs在衰老与炎症条件下的基因表达与表观遗传修饰变化；研究和筛选Foxp1基因变异在抵御关节骨骼干细胞(SSCs)的衰老与免疫抑制反应，促进关节再生修复过程中的潜在作用；通过荧光报告细胞系筛选小分子库，以期开发能靶向SSCs抗衰老与免疫抑制的先导化合物。我们的研究对于开发骨关节炎的治疗药物，都有非常重要的意义

Osteoarthritis is a degenerative symptom characterized with articular cartilage degeneration and local inflammation. Skeletal stem cells (SSCs) that reside at the superfacial zone of articular cartilage account for its homeostasis and regeneration through self-renewal and chondrogenic differentiation, as well as its immunorepressive function. The regenerative capacity of SSCs declines with age and inflammation. Our previous study has shown that transcription factor Foxp1 regulates SSCs senescence and prevents osteoporosis through directly repression p16 transcription. In this study, we aim to investigate the molecular mechanisms controlling the SSCs senescence and anti-inflammation reaction. The research tasks include genetic and epigenetic expression profiles of SSCs at condition of aging and inflammation using lineage tracing and reporter mice; exploring Foxp1 variants that potentially resistant to SSCs senescence and inflammation and facilitating cartilage regeneration; screening small molecule that protects SSCs from senescence and inflammation based on luciferase reporter cells. Our research would be of significance to understanding the mechanisms of SSCs rejuevenation and immunorepression, shedding new light into the developing therapeutic strategy for osteoarthritis.