TGF-β2对下颌髁状突软骨及胫骨生长板软骨生长及损伤修复作用的实验研究

Mandibular condyle is the important growth region of mandible,the growth plate cartilage is the growth center of long bone.Although both of them are endochondral ossification,it is not clear about the mechanism of growing and wound healing.Growth factor is closely related to the growth 、signal transduction of cartilage cells and the process for wound healing of cartilage.It is payed more attention to the effective of TGF-β2 to growth and wound healing upon both Mandibular condylar cartilage and growth plate cartilage.The purpose of this research is to observed the influence of endogenous and exogenous TGF-β2 to their growth characteristics and signal transduction, via establishing vitro modle of the cartilage cells and cartilage of mandibular condylar and tibial growth plate,;The research also includes establishment the model of TGF-β2 gene transfection cartilage cells and observed the influence of their growth characteristics and signal transduction after enhancing the expression of TGF-β2;Finally ,establishment of the model for the injury and reciprocal transplant between condylar cartilage and tibial growth plate cartilage,the aim is to observe the growth effective of cartilage after reciprocal transplant and effect of the exogenous TGF-β2 to wound healing of cartilage.The objective is to clarify the effects of TGF-β2 in growth and wound healing of condylar and tibial growth plate cartilage, providing the experimental evidence for prevention and treament of articular cartilage diseases.

下颌髁状突为下颌骨的重要生长区，而生长板软骨是长骨的生长中心，虽然二者均为软骨内成骨，但二者在生长中的机制及对损伤修复的作用还未完全阐明。软骨的生长、与生长相关的信号转导及软骨损伤修复的过程与生长因子的作用密不可分。TGF-β2对髁状突软骨及胫骨生长板软骨生长及损伤修复作用越来越受到关注。本课题旨在建立髁状突和胫骨生长板软骨的细胞及软骨体外培养模型，探讨内、外源性TGF-β2对二者生长特性及信号转导的影响；通过TGF-β2基因转染髁状突软骨细胞及胫骨生长板软骨细胞，明确TGF-β2增强表达后对软骨细胞生长特性及信号转导的影响；最后建立髁状突软骨和胫骨生长板软骨的损伤及交互移植动物模型，研究软骨交互移植后生长变化，明确外源性TGF-β2对软骨损伤修复的影响。通过研究揭示 TGF-β2在髁状突软骨及胫骨生长板软骨生长及损伤修复中的作用机理，以期为关节软骨疾病的预防、治疗提供实验依据。

颞下颌关节是人体内最复杂的关节之一，具有非常重要的生理和研究意义。髁突作为其重要组成部分，是下颌骨的生长中心，受到多种生长因子、细胞因子、内外环境等因素影响，并由多条信号通路在时间和空间上相互交叉调控。依靠本项目资助，我们主要研究了外源性TGF-β2及内源性TGF-β2对髁突软骨细胞增殖分化、基质形成及信号转导的影响；下颌髁突软骨及胫骨生长板软骨交互移植后软骨生长特性的变化；以及炎症因子对髁突软骨细胞生物学特性的影响。通过系列实验表明：TGF-β2具有促进髁突软骨细胞生长和相关基质形成的作用；胫骨生长板的移植有助于髁突软骨缺损后的修复；IL-1β刺激髁突软骨细胞后能建立稳定的炎症模型，导致软骨细胞表型的丧失，TGF-β信号通路在其中具有重要的调控作用；IL-1β可通过miR-140-5p调控软骨的形成分化过程，其中Smad3是miR-140-5p调节TGF-β信号通路中的重要靶基因。本研究揭示了TGF-β信号通路在髁突软骨的表型维持、炎症调控中的重要作用，为深入研究髁突软骨生物学特性及炎症应答机制奠定基础，以期为阐明颞下颌关节炎的病损机制提供新的思路。