Dihydrotestosterone and 17β-estradiol modulate TMJ osteoarthritis development and reveal sex-specific differences in pathogenesis
Abstract 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 st...
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Nature Portfolio
2025-05-01
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| Online Access: | https://doi.org/10.1038/s41598-025-03475-w |
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| author | Takuma Tomura Takenobu Ishii Norio Kasahara Yasushi Nishii |
| author_facet | Takuma Tomura Takenobu Ishii Norio Kasahara Yasushi Nishii |
| author_sort | Takuma Tomura |
| collection | DOAJ |
| description | Abstract 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. |
| format | Article |
| id | doaj-art-9869886a11084f8a8be0d4cb52781bbd |
| institution | OA Journals |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-05-01 |
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| spelling | doaj-art-9869886a11084f8a8be0d4cb52781bbd2025-08-20T02:03:31ZengNature PortfolioScientific Reports2045-23222025-05-0115111110.1038/s41598-025-03475-wDihydrotestosterone and 17β-estradiol modulate TMJ osteoarthritis development and reveal sex-specific differences in pathogenesisTakuma Tomura0Takenobu Ishii1Norio Kasahara2Yasushi Nishii3Department of Orthodontics, Tokyo Dental CollegeDepartment of Orthodontics, Tokyo Dental CollegeDepartment of Histology and Developmental Biology, Tokyo Dental CollegeDepartment of Orthodontics, Tokyo Dental CollegeAbstract 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.https://doi.org/10.1038/s41598-025-03475-wTemporomandibular jointOsteoarthritis17β-EstradiolDihydrotestosteroneAromataseMechanical stress |
| spellingShingle | Takuma Tomura Takenobu Ishii Norio Kasahara Yasushi Nishii Dihydrotestosterone and 17β-estradiol modulate TMJ osteoarthritis development and reveal sex-specific differences in pathogenesis Scientific Reports Temporomandibular joint Osteoarthritis 17β-Estradiol Dihydrotestosterone Aromatase Mechanical stress |
| title | Dihydrotestosterone and 17β-estradiol modulate TMJ osteoarthritis development and reveal sex-specific differences in pathogenesis |
| title_full | Dihydrotestosterone and 17β-estradiol modulate TMJ osteoarthritis development and reveal sex-specific differences in pathogenesis |
| title_fullStr | Dihydrotestosterone and 17β-estradiol modulate TMJ osteoarthritis development and reveal sex-specific differences in pathogenesis |
| title_full_unstemmed | Dihydrotestosterone and 17β-estradiol modulate TMJ osteoarthritis development and reveal sex-specific differences in pathogenesis |
| title_short | Dihydrotestosterone and 17β-estradiol modulate TMJ osteoarthritis development and reveal sex-specific differences in pathogenesis |
| title_sort | dihydrotestosterone and 17β estradiol modulate tmj osteoarthritis development and reveal sex specific differences in pathogenesis |
| topic | Temporomandibular joint Osteoarthritis 17β-Estradiol Dihydrotestosterone Aromatase Mechanical stress |
| url | https://doi.org/10.1038/s41598-025-03475-w |
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