骨损伤微环境下TGF-β/JNK通路介导骨骼干细胞调控骨锚钉成骨愈合的机制研究

肩袖等肌腱韧带损伤高发且难以自愈，缝合锚钉是手术修复首选内植物，但可吸收等材料锚钉费用贵且失败率仍较高。我们前期以人同种异体皮质骨为材料研发出系列新型骨锚钉，动物实验结果满意，但部分存在成骨量不足，密度持续下降的“空心化”问题。前期研究及最新报道表明骨骼干细胞在骨损伤微环境下具有增殖分化为成骨细胞的潜能，同时可自表达TGF-β。而TGF-β/JNK通路可显著调节成骨细胞活性。据此推测新机制：骨骼干细胞激活后可定向分化为成骨细胞，并通过自表达TGF-β/JNK通路调节成骨细胞活性和成骨愈合。本课题拟以野生小鼠建立肩袖损伤骨锚钉修复模型，通过骨骼干细胞转基因荧光标记及活性抑制小鼠、TGF-β基因敲除小鼠、JNK基因敲除小鼠，从组织学、基因敲除动物和离体细胞三个层面，进行多靶点干预，深入研究骨骼干细胞-TGF-β/JNK-成骨细胞通路，有望阐明骨锚钉调控机制，为临床转化提供理论依据。

Rotator cuff and other tendon and ligament injuries are high and difficult to heal. Suture anchors are the first choice for surgical repair, but the absorbable materials such as anchors are expensive and the failure rate is still high. In the early stage, we used human allogeneic cortical bone as material to develop a series of new bone anchors, and the results of animal experiments were satisfactory, but some of them had the problem of "hollowing out" with insufficient osteogenesis and continuous decrease in density. Previous studies and latest reports have shown that skeletal stem cells have the potential to proliferate and differentiate into osteoblasts in bone injury microenvironment and can self-express TGF- β at the same time. TGF- β / JNK pathway can significantly regulate the activity of osteoblasts. Based on this, we speculate a new mechanism: skeletal stem cells can differentiate into osteoblasts after activation, and regulate osteoblast activity and osteogenic healing through self-expression of TGF- β / JNK pathway. In this study, the rotator cuff injury model of bone anchor repair was established in wild mice. Through skeletal stem cell transgene fluorescence labeling and activity inhibition mice, TGF- β gene knockout mice and JNK gene knockout mice, multi-target intervention was carried out from the three levels of histology, gene knockout animals and in vitro cells, and the skeletal stem cell-TGF- β / JNK- osteoblast pathway was deeply studied, which is expected to clarify the regulation mechanism of bone anchor. To provide theoretical basis for clinical transformation.