Sex differences in the estrogen-dependent regulation of temporomandibular joint remodeling in altered loading.
Sex differences in the estrogen-dependent regulation of temporomandibular joint remodeling in altered loading.
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DOI：
10.1016/j.joca.2016.11.008
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发表时间：
2017-04
影响因子：
7
通讯作者：
Wadhwa S
中科院分区：
文献类型：
--
作者：
Robinson JL;Cass K;Aronson R;Choi T;Xu M;Buttenbaum R;Drissi H;Lu HH;Chen J;Wadhwa S
颞下颌关节 (TMJ) 疾病主要困扰女性，表明雌激素在该疾病病因中发挥着重要作用。此前，我们确定减少咬合负荷 (DOL) 会抑制雌性野生型 (WT) 小鼠下颌髁突软骨 (MCC) 中 II 型胶原蛋白 (Col2) 的表达，而在雄性小鼠中未观察到任何变化。女性雌激素受体β（ERβ）缺乏消除了软骨形成的减少。因此，本研究的目的是检查雌二醇 - ERβ 信号在介导雄性小鼠 DOL 效应中的作用，以进一步破译性别差异。用安慰剂或雌二醇治疗 21 日龄雄性 WT 和 ERβKO 雄性小鼠，并暴露于正常或 DOL 中 4 周。完成软骨厚度和细胞增殖、软骨形成标志物和雌激素受体α (ERα) 的基因表达和免疫组织化学，以及通过 microCT 进行的骨组织形态计量学分析，以确定雌二醇对 DOL 对 TMJ 影响的影响。 ERβKO 雄性小鼠缺乏 MCC 表型。在两种基因型中，雌二醇治疗均增加了 Col2 基因表达和小梁厚度。 DOL 与雌二醇联合治疗导致两种基因型的 Col2 基因表达显着增加。 DOL 诱导的 Col2 表达抑制的性别差异似乎不是由雄性和雌性小鼠之间雌二醇水平的差异介导的。为了破译颞下颌关节疾病的性别二态性，更好地了解雌激素的作用和改变负荷至关重要。
Temporomandibular joint (TMJ) diseases predominantly afflict women, suggesting a role of estrogen in the disease etiology. Previously, we determined that decreased occlusal loading (DOL) inhibited collagen type II (Col2) expression in the mandibular condylar cartilage (MCC) of female wild-type (WT) mice whereas no change was observed in males. This decrease in chondrogenesis was abolished by estrogen receptor beta (ERβ) deficiency in females. Therefore, the goal of this study was to examine the role of estradiol – ERβ signaling in mediating DOL effects in male mice to further decipher sex differences. Male 21 day-old WT and ERβKO male mice were treated with either placebo or estradiol and exposed to normal or DOL for 4 weeks. Cartilage thickness and cell proliferation, gene expression and immunohistochemistry of chondrogenic markers and estrogen receptor alpha (ERα), and analysis of bone histomorphometry via microCT were completed to ascertain the effect of estradiol on DOL effects to the TMJ. ERβKO male mice lack a MCC phenotype. In both genotypes, estradiol treatment increased Col2 gene expression and trabecular thickness. DOL in combination with estradiol treatment caused a significant increase in Col2 gene expression in both genotypes. The sex differences in DOL-induced inhibition of Col2 expression do not appear to be mediated by differences in estradiol levels between male and female mice. Greater understanding on the role of estrogen and altered loading are critical in order to decipher the sex dimorphism of TMJ disorders.