Objective

To observe and analyze the interaction between excessive mechanical stress (MS) and decreased sex hormones on Temporomandibular Joint Osteoarthritis (TMJ-OA), and to discover TMJ-OA disease susceptibility genes by molecular biological analysis to elucidate part of the mechanism of TMJ-OA onset.

Design

For experimental groups, orchiectomy (ORX) or ovariectomy (OVX) was performed on sexually mature 8-week-old mice. A metal plate was attached to the posterior surface of the maxillary incisors to apply excessive MS on mandibular condyles. Male mice were divided into control, ORX, MS, and ORX + MS groups, while female mice were divided into control, OVX, MS, and OVX + MS groups. Mandibular condyles were evaluated by histology and molecular biology.

Results

Histomorphometric analysis of the TMJ in ORX + MS and OVX + MS groups revealed the thinnest chondrocyte layers, highest modified Mankin scores, and significant increases in the number of osteoclasts. Gene expression analysis indicated upregulation of Angptl7 and Car1 genes in the mandibular condyles of mice subjected to the combined effects of excessive MS and reduced sex hormones. In vitro analysis suggested that cartilage-like cells overexpressing Angptl7 enhanced calcification, and osteoblast-like cells overexpression Car1 suppressed cell proliferation and calcification.

Conclusions

A severe TMJ-OA mouse model was successfully developed by applying excessive MS on the mandibular condyle of male and female mice with reduced sex hormones. Disease-susceptibility genes Angptl7 and Car1 were newly discovered in the experimental groups, suggesting their involvement in the onset mechanism of TMJ-OA.

中文翻译：

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机械应力及双氢睾酮或17β-雌二醇缺乏对小鼠颞下颌关节骨关节炎的影响

客观的

观察分析过度机械应力（MS）与性激素降低对颞下颌关节骨关节炎（TMJ-OA）的相互作用，通过分子生物学分析发现TMJ-OA疾病易感基因，阐明TMJ-OA的部分发病机制。发作。

设计

对于实验组，对性成熟的 8 周龄小鼠进行睾丸切除术 (ORX) 或卵巢切除术 (OVX)。将金属板连接到上颌切牙的后表面，以在下颌髁上施加过多的 MS。雄性小鼠分为对照、ORX、MS和ORX+MS组，雌性小鼠分为对照、OVX、MS和OVX+MS组。通过组织学和分子生物学评估下颌骨髁。

结果

ORX + MS 和 OVX + MS 组中 TMJ 的组织形态学分析显示，软骨细胞层最薄，改良 Mankin 评分最高，破骨细胞数量显着增加。基因表达分析表明，受到过度 MS 和性激素减少的综合影响的小鼠下颌骨髁中Angptl7和Car1基因的上调。体外分析表明，过表达Angptl7的软骨样细胞增强了钙化，过表达Car1的成骨细胞样细胞抑制了细胞增殖和钙化。

结论

通过在雄性和雌性小鼠的下颌髁上应用过量的 MS 并减少性激素，成功地建立了严重的 TMJ-OA 小鼠模型。实验组新发现疾病易感基因Angptl7和Car1 ，提示它们参与了TMJ-OA的发病机制。