槲皮素调控骨软骨缺损一体化修复及机制研究

The temporomandibular joint defects are usually cartilage, accompanying with subchondral bone, defects. Therefore, the key point for repairing the temporomandibular joint defects is to fulfill the osteochondral formation at the same period. The most difficult parts for doing so are how to suppress the local inflammation in the defect site and inhibit the dedifferentiation and maintain the chondrogenesis of chondrocytes under the inflammation micro-environment. In addition, how to promote the osteogenesis of bone marrow stromal cells (BMSCs) during the repairing of subchondral bone defects is also critical. Our previous studies have revealed that quercetin induced the osteogenesis of BMSCs and the expression of cartilage factors and inhibited the expression of inflammatory factors of chondrocytes as well, indicating that the quercetin might inhibit the dedifferentiation and maintain the chondrogenesis of chondrocytes under the inflammation micro-environment, and cause the bi-directional differentiation of BMSCs-chondrocytes. However, the underlying mechanisms for quercetin regulation are still remain unclear. The aim of this study is to investigate the regulation effects of quercetin on the bi-directional differentiation of BMSCs-chondrocytes, and the dedifferentiation of chondrocytes under inflammation micro-environment, as well as to illuminate the underlying mechanisms. Meanwhile, by loading quercetin onto the osteochondral integrated bilayered scaffolds for constructing the tissue engineered bone-cartilage, the current project will provide a new method and strategy for repairing maxillofacial osteochondral defects.

颞下颌关节缺损通常为软骨伴软骨下骨缺损。实现骨软骨一体化修复是颞下颌关节缺损修复的关键。其难点在于如何抑制缺损部位的炎症反应及软骨细胞去分化、并维持其成软骨分化，同时实现软骨下骨缺损部位骨髓基质干细胞（BMSCs）成骨分化。课题组新近研究发现槲皮素具有良好的调控BMSCs成骨分化并促进骨缺损修复功能，预实验发现槲皮素能够促进软骨细胞成软骨分化、并抑制其炎症因子表达。表明槲皮素可能具有抑制炎症微环境下软骨细胞去分化、并维持其定向成软骨分化作用，及调控BMSCs-软骨细胞成骨/成软骨双向分化功能。然而，其具体作用规律和机制仍有待进一步研究。本课题旨在系统研究槲皮素的成骨/成软骨双向调控、及其抑制炎症环境下软骨细胞的去分化作用，揭示内在生物学效应和机制。同时，将槲皮素负载于骨软骨一体化双层支架材料构建组织工程骨软骨，从而为颌面部骨软骨缺损的一体化修复提供新的方法和策略。

颞下颌关节缺损通常为软骨伴软骨下骨缺损。实现骨软骨一体化修复是颞下颌关节缺损修复的关键。在课题组前期研究及预实验基础上，本项目证明在正常及炎症微环境下槲皮素具有维持软骨细胞表型、抑制其炎症作用，其细胞学作用与AKT、P65信号通路及巨噬细胞极化作用相关。同时，通过大鼠膝关节炎模型证明槲皮素具有抑制骨关节炎、促进体内炎症环境下软骨修复的作用。此外，本项目成功制备负载槲皮素的骨软骨一体化双层支架材料，并将此新型支架材料应用于兔膝关节缺损动物模型，证实其具有良好的体内骨软骨修复效果。依托本项目，课题组发表SCI论文4篇，会议论文2篇；申请发明专利1项；参加国内学术会议3次；培养硕士研究生2名，博士研究生1名。本项目的实施为实现颞下颌关节骨软骨缺损一体化精准修复的支架材料的设计奠定基础，从而为颞下颌关节缺损功能性修复提供新的方法及策略，具有重要的科学意义和临床应用价值。