Hedgehog信号通路在肌腱损伤后修复及钙化发生中的作用及机制研究

临床中尚无能够同时促进肌腱修复且抑制肌腱钙化的方法，肌腱修复与钙化的调控机制不明。我们前期研究提示：损伤源性肌腱祖细胞为促进肌腱修复及抑制钙化的细胞水平靶点；肌腱损伤后，修复过程与钙化形成存在共同调控机制。前期体内及体外预实验结果提示：肌腱损伤后，Hedgehog通路上调；Hedgehog通路激动剂下调肌腱相关标志物基因及蛋白表达，上调软骨/骨相关标志物基因及蛋白表达；Hedgehog通路抑制剂上调肌腱相关标志物基因及蛋白表达，同时下调软骨/骨相关标志物基因及蛋白表达。推测：肌腱损伤后，Hedgehog通路抑制损伤源性肌腱祖细胞的成肌腱分化同时促进其成软骨/骨分化，从而抑制肌腱修复（瘢痕愈合）同时促进肌腱钙化发生；抑制Hedgehog信号通路可以促进肌腱修复同时抑制肌腱钙化。本项目旨在阐明Hedgehog通路在肌腱损伤后修复及钙化发生中的作用及机制，探索靶向促进肌腱修复并抑制钙化的新药物。

There is no specific method to promote tendon repair and inhibit tendon calcification simultaneously in clinic, and the regulatory mechanism of tendon repair and calcification is unknown. Our previous studies suggest that the injured tendon-derived progenitor cells (inTPCs) is the cell level target for promoting tendon repair and inhibiting calcification, and there is a common regulatory mechanism in repair process and calcification formation after tendon injury. Our in vivo and in vitro preliminary experiments showed that hedgehog pathway was up-regulated after tendon injury; hedgehog pathway agonist down regulated gene and protein expression of tendon related markers and up regulated gene and protein expression of cartilage / bone related markers; hedgehog pathway inhibitor up regulated gene and protein expression of tendon related markers and down regulated gene and protein expression of cartilage / bone related markers. It is speculated that after tendon injury, hedgehog pathway may inhibit the tenogenic differentiation of injured tendon progenitor cells and promote their chondrogenic / osteogenic differentiation, so as to inhibit tendon repair (scar healing) and promote tendon calcification; inhibition of hedgehog signaling pathway may promote tendon repair and inhibit tendon calcification. The purpose of this project is to elucidate the effect and mechanism of hedgehog pathway in tendon repair and calcification after tendon injury, and to explore new drugs targeting to promote tendon repair and inhibit calcification.