Tomura Takuma, Ishii Takenobu, Kasahara Norio, Nishii Yasushi
Department of Orthodontics, Tokyo Dental College, 2-9-18 Kandamisaki- cho, Chiyoda-ku, Tokyo, 101-0061, Japan.
Department of Histology and Developmental Biology, Tokyo Dental College, 2-9-18 Kandamisaki-cho, Chiyoda-ku, Tokyo, 101-0061, Japan.
Sci Rep. 2025 May 28;15(1):18740. doi: 10.1038/s41598-025-03475-w.
To investigate the effects and mechanisms of dihydrotestosterone (DHT) and 17β-estradiol on temporomandibular joint osteoarthritis (TMJ-OA) to understand sex differences and apply findings to TMJ-OA prevention and treatment. Ten-week-old male C57BL/6J mice were divided into six groups to study the effects of mechanical stress (MS), aromatase inhibitors (Ai), orchiectomy (ORX), and 17β-estradiol supplementation on TMJ-OA. Interventions included mechanical stress induction and hormone manipulations. Analyses included serum hormone levels, micro-CT, histomorphometry, immunohistochemistry, RT-qPCR for gene expression, and statistical evaluations. ORX and Ai-induced reductions in DHT and 17β-estradiol caused bone loss, including decreased BV/TV and trabecular thickness, and increased trabecular spacing. MS further reduced cartilage thickness, Safranin O-positive areas, and increased osteoclast counts. Matrix metalloproteinase-13(MMP13) and a disintegrin and metalloproteinase with thrombospondin motifs 5 (ADAMTS5) levels were highest in MS + Ai and MS + Ai + ORX groups. In contrast, 17β-estradiol supplementation restored cartilage thickness, reduced osteoclast activity, suppressed inflammatory markers (NFκB, Gremlin 1, RelA), and increased BMP7 expression. The lower incidence of TMJ-OA in males may result from testosterone and DHT being converted to 17β-estradiol by adrenal aromatase, mitigating mechanical stress effects and protecting the temporomandibular joint via the Gremlin-1-NF-κB pathway.
研究二氢睾酮（DHT）和17β-雌二醇对颞下颌关节骨关节炎（TMJ-OA）的影响及机制，以了解性别差异并将研究结果应用于TMJ-OA的预防和治疗。将10周龄雄性C57BL/6J小鼠分为六组，研究机械应力（MS）、芳香化酶抑制剂（Ai）、去势（ORX）和补充17β-雌二醇对TMJ-OA的影响。干预措施包括机械应力诱导和激素操作。分析包括血清激素水平、显微CT、组织形态计量学、免疫组织化学、基因表达的RT-qPCR以及统计学评估。ORX和Ai导致的DHT和17β-雌二醇减少引起骨质流失，包括骨体积分数（BV/TV）和小梁厚度降低，以及小梁间距增加。MS进一步降低了软骨厚度、番红O阳性区域，并增加了破骨细胞数量。基质金属蛋白酶-13（MMP13）和含血小板反应蛋白基序的解聚素和金属蛋白酶5（ADAMTS5）水平在MS+Ai和MS+Ai+ORX组中最高。相比之下，补充17β-雌二醇可恢复软骨厚度，降低破骨细胞活性，抑制炎症标志物（NFκB、Gremlin 1、RelA），并增加骨形态发生蛋白7（BMP7）的表达。男性TMJ-OA发病率较低可能是由于睾酮和DHT被肾上腺芳香化酶转化为17β-雌二醇，减轻了机械应力的影响，并通过Gremlin-1-NF-κB途径保护颞下颌关节。
