炎症导致颞下颌关节盘退行性变的机制及关节盘移位的探讨

Disc displacement is the most common clinical subtypes of temporomandibular disorders, but the specific mechanism is unknown. Most scholars believe that: disc displacement causes the deformation, often accompanied with inflammation and pain. However, our early studies about cadavers found that part of the deformation of the TMJ disc associated with synovial inflammation, without displacement; our previous animal studies found that induced chronic inflammation of TMJ resulted in degeneration of disc, including thickening and deformation; besides, chronic inflammation of TMJ could lead to deterioration of mechanical properties, including decrease of the tensile and compression modulus. Therefore, our research group proposed an innovative theory: inflammation may be the key factor leading to TMJ disc displacement through leading to degeneration of the disc and disturbing the coordination of the disc condyle complex.. Based on the previous research, this project is to explore the mechanism of inflammation leading to disc degeneration from multi-level: the articular disc ultrastructure, biomechanical properties, stromal cells and related molecular signal pathway. In vivo and in vitro experiments will be performed to test effects of chronic inflammation of TMJ on ultrastructure and biomechanical properties of disc collagen fiber; to discuss whether inflammation could activate the NF-κB signaling pathway and regulate function of disc fibroblasts; to test whether the effect of inflammation on fibroblasts and collagen fibers could be reversed by blocking NF-κB signaling pathway. We hope to explain TMJ disc degeneration by establishing the connection among inflammation, fibroblast dysfunction and collagen fiber ultrastructure and elastic modulus, which might even provide new ideas for disc displacement.

关节盘移位是颞下颌关节紊乱病最常见的亚型，但机制不明。以往认为：关节盘移位导致其变形，且常因伴发炎症而出现疼痛。然而，本课题组早期的尸检研究发现：部分关节盘变形伴滑膜炎症，但尚未移位；后期的动物实验发现：诱导TMJ慢性炎症可导致关节盘增厚、变形等退行性变；且炎症组关节盘的弹性模量显著降低。因此，本课题组提出新理论：炎症导致关节盘退行性变进而影响盘髁复合体协调运动可能是关节盘移位的关键因素。本项目拟在前期基础上，从关节盘的超微结构、生物力学性能、基质细胞功能及相关分子信号通路等多层次探讨炎症导致关节盘退行性变的机制。通过体内及体外实验，探讨慢性炎症对TMJ关节盘胶原纤维的超微结构与超微模量的影响，探讨炎症是否通过激活NF-κB信号通路调控成纤维细胞的功能。通过建立炎症、成纤维细胞功能障碍、胶原纤维超微结构及弹性模量变化的联系，探讨炎症导致关节盘退行性变的机制，为解释关节盘移位提供新思路。

关节盘移位是颞下颌关节紊乱病最常见的临床亚型，但机制不明。本项目在前期基础上，利用关节上腔注射两次CFA法建立的大鼠TMJ慢性炎症模型，通过MRI检测发现关节盘变形、外侧移位；结合体内及体外实验，发现慢性炎症可以破坏TMJ关节盘胶原纤维的超微结构并降低超微弹性模量，改变胶原纤维蛋白结构，进一步探讨机制发现炎症可通过激活NF-κB信号通路调控关节盘成纤维细胞的代谢功能，炎症可促进TMJ关节盘成纤维细胞中NF-κB 的DNA结合活性及核转位；调控成纤维细胞的分泌功能，导致胶原纤维的超微结构改变及超微弹性模量降低。关节局部注射NF-κB信号通路阻断剂（PDTC）后，关节盘微观形貌及弹性模量均得到缓解，盘变形及移位减轻。本项目揭示了炎症、成纤维细胞功能障碍、胶原纤维超微结构及弹性模量变化之间的联系，并发现NF-κB信号通路可能为临床上治疗关节盘退行性变甚至关节盘移位提供新的治疗靶点。为解释TMJ关节盘退行性变提供依据，为解释关节盘移位提供了新思路。