MODULATION OF TMJ DEGRADATION BY RELAXIN AND ESTROGEN

松弛素和雌激素对颞下颌关节退化的调节

• 批准号: 2897124
• 负责人: SUNIL D KAPILA
• 金额: $ 9.35万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 1996
• 资助国家: 美国
• 起止时间: 1996-09-15 至 2001-07-14
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2897124
• 关键词: chemical binding; collagen; collagenase; enzyme biosynthesis; estradiol; estrogens; extracellular matrix proteins; female; fibroblasts; gene expression; hormone regulation /control mechanism; joint ligament; laboratory rabbit; menstrual cycle; molecular site; mucopolysaccharides; pathologic process; pregnancy; protein biosynthesis; protein degradation; relaxin; stromelysin; temporomandibular joint syndrome; tissue /cell culture; tissue inhibitor of metalloproteinases

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.

描述：拟议研究的目的是确定 女性性激素松弛素和雌激素在 TMJ 发病机制中的作用 女性疾病。 雌激素在 TMD 中的作用已被提出，但很少有人提出 支持这一理论的确凿证据是可用的，并且潜在的 其他女性性激素在 TMD 中的作用尚未得到研究。 的 特别感兴趣的是松弛素，它仅在骑自行车时全身被发现 和孕妇，这会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 MMP 的表达 并减少真皮内TIMPs和I型胶原蛋白的合成 成纤维细胞。 初步研究表明，松弛素可增加 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，但不在滑膜细胞中，这表明椎间盘和 韧带细胞可能是基质降解的特定靶位点 松弛素效应的影响是通过事先暴露这些来增强的 细胞转化为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颞下颌关节病 减少关节盘和韧带中 MMP 的含量并减少 TIMP 和胶原蛋白的含量 细胞。 具体目标是：（1）评估剂量依赖性和时间性 松弛素对未引发和未引发的 MMP、TIMP 和 I 型胶原的调节 培养中雌激素引发的兔颞下颌关节盘和韧带细胞； (2)本地化 未引发和雌激素引发的兔 TMJ 中的松弛素结合位点和 确定 TMJ 盘和韧带的松弛素结合特性 细胞； (3)确定进入系统的全身松弛素的比例 雌激素引发的和患有关节炎的兔子； (4)考察松弛素的作用 和雌激素对组织中椎间盘胶原和糖胺聚糖损失的影响 体内外植体，并评估基质的相对贡献 合成和降解对圆盘基质的净损失。