MODULATION OF TMJ DEGRADATION BY RELAXIN AND ESTROGEN

描述：拟议研究的目的是确定 雌性激素松弛素和雌激素在颞下颌关节发病机制中的作用 女性的疾病。 雌激素在TMDs中的作用已经被提出，但很少 支持这一理论的确凿证据是可用的， 其他女性性激素在TMD中的作用尚未研究。 的 特别令人感兴趣的是松弛素，它仅在骑自行车时全身发现 和孕妇，并导致骨盆关节过度活动。 松弛素 调节子宫和宫颈组织的重塑， 月经周期和怀孕。 它还诱导MMPs的表达， 减少真皮组织中TIMP和I型胶原的合成 成纤维细胞 初步研究表明，松弛素增加 胶原酶和基质溶解素在培养的颞下颌关节盘中的表达， 韧带细胞，但不是在滑膜细胞，这表明，光盘和 韧带细胞可能是基质降解剂的特异性靶位点， 松弛素效应的影响，是加强了事先暴露这些 细胞分泌β雌二醇 拟议的研究将检验以下假设： 松弛素和雌激素通过增加表达而导致女性TMJ疾病 降低关节盘和韧带中MMP和TIMP及胶原的表达 细胞 具体目的是：（1）评价剂量依赖性和时间依赖性 松弛素对未致敏和未致敏小鼠MMPs、TIMPs和I型胶原的调节 雌激素致敏兔颞下颌关节盘和韧带细胞培养;（2）定位 松弛素结合位点在未引发和雌激素引发兔颞下颌关节和 测定颞下颌关节盘和韧带的松弛结合特性 （3）确定进入细胞的系统性松弛素的比例; 雌激素致敏兔和关节炎兔;（4）检查松弛素的作用 和雌激素对椎间盘胶原蛋白和组织中糖胺聚糖的损失 体内外植体，并评估基质的相对贡献 合成和降解到盘基质的净损失。

DESCRIPTION: The aim of the proposed studies is to identify the role of the female sex hormones relaxin and estrogen in the etiopathogenesis of TMJ disease in women. A role for estrogen in TMDs has been proposed, but little conclusive evidence to support this theory is available, and the potential role of other female sex hormones in TMDs has not been examined. Of particular interest is relaxin, which is found systemically only in cycling and pregnant women and which causes pelvic joint hypermobility. Relaxin modulates the remodeling of uterine and cervical tissues during the menstrual cycle and pregnancy. It also induces the expression of the MMPs and decreases the synthesis of TIMPs and type I collagen in dermal fibroblasts. The preliminary studies demonstrated that relaxin increases the expression of collagenase and stromalysin in cultured TMJ disc and ligament cells, but not in synoviocytes, suggesting that the disc and ligament cells may be specific target sites for the matrix-degradative effects of relaxin effects that are potentiated by prior exposure of these cells to beta estradiol. The proposed studies will test the hypothesis that relaxin and estrogen cause TMJ disease in women by increasing the expression of MMPs and decreasing that of TIMPs and collagen in joint disc and ligament cells. The specific aims are: (1) Evaluate the dose-dependent and temporal modulation of MMPs, TIMPs and type I collagen by relaxin in unprimed and estrogen-primed rabbit TMJ disc and ligament cells in culture; (2) Localize relaxin-binding sites in the unprimed and estrogen-primed rabbit TMJ and determine the relaxin-binding characteristics of TMJ disc and ligament cells; (3) Determine the proportion of systemic relaxin that accesses the estrogen-primed and arthritic rabbits; (4) Examine the effects of relaxin and estrogen on the loss of disc collagen and glycosaminoglycans in tissue explants in vivo, and evaluate the relative contributions of matrix synthesis and degradation to the net loss of disc matrices.