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Dihydrotestosterone and 17β-estradiol modulate TMJ osteoarthritis development and reveal sex-specific differences in pathogenesis
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Dihydrotestosterone and 17β-estradiol modulate TMJ osteoarthritis development and reveal sex-specific differences in pathogenesis
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Journal Article
Dihydrotestosterone and 17β-estradiol modulate TMJ osteoarthritis development and reveal sex-specific differences in pathogenesis
2025
Overview
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.
Publisher
Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
Subject
/ ADAMTS5 Protein - metabolism
/ Animals
/ Aromatase Inhibitors - pharmacology
/ Dihydrotestosterone - metabolism
/ Dihydrotestosterone - pharmacology
/ Female
/ Humanities and Social Sciences
/ Male
/ Matrix Metalloproteinase 13 - metabolism
/ Mice
/ Osteoarthritis - drug therapy
/ Science
/ Temporomandibular Joint - drug effects
/ Temporomandibular Joint - metabolism
/ Temporomandibular Joint - pathology
/ Temporomandibular Joint Disorders - metabolism
