ROLE OF FEMALE REPRODUCTIVE HORMONES IN TMJ DISEASE

本研究的总体目的是阐明女性生殖激素松弛素、雌激素和孕激素在女性颞下颌关节（TMJ）疾病发病中的作用。尽管颞下颌疾病（TMDs）具有使人衰弱的特点，而且在育龄妇女中性别偏好高达10:1，但这些疾病的病因和发病机制仍不清楚。虽然已经提出女性生殖激素，特别是雌激素的作用，但很少有证据支持这一理论。此外，其他女性生殖激素如松弛素在tmd中的潜在作用尚未得到研究。我们最近证明松弛素通过增加基质金属蛋白酶、胶原酶和基质溶解素的表达，在培养的TMJ椎间盘细胞中诱导基质降解表型。用-雌二醇刺激细胞会使它们对松弛素的反应增加10倍。此外，我们对有或无TMJ疾病症状的女性进行的初步研究表明，与对照组或症状较轻的女性相比，有最严重TMJ疾病表现的女性血清松弛素和β -雌二醇水平最高。此外，有症状妇女报告既往妊娠的比例（44%对10.5%）和平均妊娠次数（0.8对0.1）均显著高于无症状妇女（P <或等于0.02）。尽管这些研究表明松弛素与β -雌二醇可能导致或诱发TMJ疾病，但需要进一步的证据来确定这些激素与TMJ疾病之间的明确联系。因此，通过对有症状和无症状妇女的病例对照研究设计和对孕妇的纵向前瞻性研究设计，我们将检验松弛素、β -雌二醇和孕酮的绝对水平或相对平衡的扰动是否易使育龄妇女患TMJ疾病。为了提供一种无创、更有效、更便宜的血清松弛素检测替代方法，我们还将确定唾液中的松弛素水平是否与血清中的松弛素水平相关。总之，我们的人类和基础科学研究可能有助于确定TMJ疾病的潜在激素病因，并且可能对设计针对女性这些疾病的特定诊断分析和生物学合理治疗至关重要。

The overall purpose of the proposed studies is to elucidate the role of the female reproductive hormones relaxin, estrogen and progesterone in the etiopathogenesis of temporomandibular joint (TMJ) disease in women. Despite the debilitating nature of temporomandibular disorders (TMDs) and a gender predilection as high as 10:1 in women mainly in their reproductive age, the etiology and pathogenesis of these disorders remain unknown. Although a role for female reproductive hormones, particularly estrogen, has been proposed, little evidence in support of this theory has been presented. Additionally, the potential role of other female reproductive hormones such as relaxin in TMDs has not been examined. We have recently demonstrated that relaxin induces a matrix- degradative phenotype in cultured TMJ disc cells by increasing the expression of the matrix metalloproteinases collagenase and stromelysin. Priming of the cells with beta-estradiol produces a 10-fold increase in their responsiveness to relaxin. Furthermore, our preliminary studies of women with or without symptoms of TMJ disorders reveal that women with the most severe manifestations of TMJ disease have the highest serum levels of relaxin and beta-estradiol as compared to controls or women with less severe manifestations of the disease. Additionally, both the proportion of women reporting previous pregnancies (44% versus 10.5%) and the mean number of pregnancies (0.8 versus 0.1) were significantly greater (P less than or equal to 0.02) in symptomatic than in asymptomatic women. Although these studies suggest that relaxin together with beta-estradiol may cause or predispose to TMJ disease, further evidence is needed to establish a definitive link between these hormones and TMJ disease. Therefore, using a case control study design on symptomatic and asymptomatic women and a longitudinal prospective study design on pregnant women, we will test the hypothesis that perturbations in the absolute levels or the relative balance of relaxin,beta-estradiol and progesterone predispose to TMJ disease in women of reproductive age. In order to provide a basis for a non-invasive, more efficient and less expensive alterative to relaxin assays on serum, we will also determine whether relaxin levels in saliva correlate with those in serum. Together, our human and basic sciences investigations may help to identify the potential hormonal etiology of TMJ disease, and may be critical in designing specific diagnostic assays and biologically rational therapies for these diseases in women.