半月板祖细胞标记基因CD146调控PI3K/AKT信号通路促进半月板损伤修复的作用机制

半月板损伤后良好的修复具有重要意义，但其调控分子机制暂不清楚。我们前期创新性的鉴定了半月板祖细胞的存在，并发现CD146是半月板祖细胞的标记基因且参与半月板损伤修复，进一步研究发现在CD146+半月板细胞中PI3K/AKT信号通路被激活且受到CD146的调控，而PI3K/AKT信号通路在半月板损伤修复过程中也被激活并具有促进细胞增殖和促进软骨与纤维组织形成的作用。基于此，我们提出科学假说：半月板损伤后，半月板祖细胞标记基因CD146表达上调并激活PI3K/AKT信号通路，从而在半月板损伤修复过程的增生期促进细胞增殖，在塑形期促进软骨和纤维组织生成，最终促进半月板损伤修复。因此，本项目拟通过体内外实验从基因-细胞-组织的层面阐明CD146与PI3K/AKT信号通路在半月板损伤修复过程中的调控机制，并利用这一机制探究促进半月板损伤修复的新方法，为解决半月板无血供区损伤后难以修复这一难题提供新思路。

Satisfactory repair after meniscus injury is very important, but the molecular mechanism of meniscus injury repair is not clear. Our previous study innovatively identified the presence of meniscus progenitor cells and found that CD146 was their marker gene and involved in the meniscus injury repair process. Further studies showed PI3K/AKT signaling pathway in CD146+ meniscus cells was activated and regulated by CD146, and PI3K/AKT signaling pathway was also activated during meniscus injury repair for promoting cell proliferation and formation of cartilage and fibrous tissue. Accordingly, we propose our hypothesis, while meniscus injury happened, the expression of meniscus progenitor marker gene CD146 increased and activating PI3K/AKT signaling pathway, thereby promoting cell proliferation in the proliferative stage, and promoting cartilage and fibrous tissue formation in the plastic stage, and finally promoting meniscus injury repair. Therefore, our study sought to illuminate the regulatory mechanism of CD146 and PI3K/AKT signaling pathway in meniscus injury repair process from the gene-cell-tissue level through in vitro and in vivo experiments, and then using this mechanism to explore new method for promoting meniscus injury repair, thus solving the issue of meniscus avascular area injury repair.