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<p>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 (<i>NFκB</i>,<i> Gremlin 1</i>,<i> RelA</i>), and increased <i>BMP7</i> 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 <i>Gremlin-1-NF-κB</i> pathway.</p>

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Dihydrotestosterone and 17β-estradiol modulate TMJ osteoarthritis development and reveal sex-specific differences in pathogenesis

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年5月28日

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  • Takuma Tomura,
  • Takenobu Ishii,
  • Norio Kasahara,
  • Yasushi Nishii

摘要

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.