雌激素对颞下颌关节骨关节炎作用的研究

Temporomandibular joint osteoarthritis (TMJOA) is an important subtype of temporomandibular disorders (TMD),and is common in dental clinic. There is significant sex difference in TMJOA; the prevalence in female is at least twice more than that in male; however, the associated mechanism is still unclear. Our group has been exploring the effect of estrogen on TMD, and has established TMJOA rat model by intraarticular injection of Monosodium Iodoacetate (MIA). In the present study, female Sprague-Dawley rats were used to establish TMJOA model or for primary chondrocyte culture. The effects of E2 in several levels on TMJOA were evaluated by pain associated behavioral test, histopathology and Micro CT; and expressions of metabolism related genes of chondrocyte, including MMPs, and proapoptotic genes, including Fas, were evaluated by molecular biological analysis. Estrogen receptor antagonist ICI 182780 was used to evaluate whether the effect of estrogen on MIA-induced TMJOA could be alleviated. In the present study, we aim to examine the effects of estrogen on TMJOA and the associated mechanism in an TMJOA rat model, and we may provide a novel inspect into the pathogenesis of sex difference in TMJOA and potential therapeutic interventions.

颞下颌关节骨关节炎（TMJOA）是口腔临床常见病，为颞下颌关节紊乱病的重要亚型之一；其发病存在明显的性别差异，女性TMJOA发病率至少是男性2倍，但机制不明。本课题组一直致力于探讨雌激素对颞下颌关节紊乱病（TMD）的作用，并通过关节内注射碘醋酸钠（MIA）成功建立了大鼠TMJOA模型。本项目拟利用雌性SD大鼠，在MIA诱导的TMJOA模型和原代培养的软骨细胞中，采用疼痛行为学、组织病理学、Micro CT等方法，评价不同剂量雌激素对TMJOA中髁突软骨及骨破坏的作用；采用分子生物学方法评价雌激素对MMPs等髁突软骨细胞代谢及Fas等细胞凋亡相关基因表达的影响；并通过应用雌激素受体阻断剂ICI 182780，分析雌激素对TMJOA的调控能否被阻断。本研究旨在探讨雌激素对TMJOA的作用及其相关机制,更好地理解TMJOA的性别差异，并为临床治疗该疾病提供新的靶点。

本项目严格按计划执行，通过利用雌性SD大鼠，在MIA诱导的TMJOA 模型和原代培养的软骨细胞中，采用组织病理学、Micro CT 等方法，评价不同剂量雌激素对 TMJOA 中髁突软骨及骨破坏的作用；采用分子生物学方法评价雌激素对 MMPs 等髁突软骨细胞代谢及Fas等细胞凋亡相关基因表达的影响；并通过应用雌激素受体阻断剂 ICI 182780，分析雌激素对 TMJOA 的调控的影响。结果显示：雌激素可以剂量依赖性地加重大鼠TMJOA，阻断雌激素受体可部分抑制 MIA 诱导 TMJOA 及 E2 对 TMJOA 的加重作用；雌激素可促进软骨细胞中 Fas 等凋亡相关基因的表达，但 对 MMP3 等软骨代谢相关基因无明显影响。这为探讨雌激素调控TMJOA的相关机制，以及解释临床中女性易患TMJOA奠定了坚实基础。