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Here, we aim to determine whether androgen is protective against inflammatory-erosive disease in TNF-transgenic (TNF-Tg) mice.<\/jats:p>\n               <jats:p>Wild-type (WT) and TNF-Tg male mice underwent sham (WT, n = 3; TNF-Tg, n = 7) or orchiectomy (WT, n = 3; TNF-Tg, n = 7) surgery at 1 month old to remove androgen production confirmed by serum testosterone concentration. Cohorts of orchiectomized TNF-Tg males were treated with either 5\u0251-dihydrotestosterone (.025\u2005mg\/day) (n = 3) or placebo (n = 3) via subcutaneous pellet insertion. Weekly clinical measures, along with mid-hindpaw bone volumes and ankle histology at 3 months old were evaluated for all groups.<\/jats:p>\n               <jats:p>Orchiectomies in TNF-Tg males significantly decreased serum testosterone (P &amp;lt; .05), weight gain (P &amp;lt; .001), and mid-hindpaw bone volumes (P &amp;lt; .05) in comparison to sham TNF-Tg mice. The cuboid bone also had increased synovitis by histology with the loss of androgen (P &amp;lt; .05). Treatment of orchiectomized TNF-Tg males with 5\u0251-dihydrotestosterone protected against the changes in weight gain (P &amp;lt; .01) and bone erosion (P &amp;lt; .05) associated with decreased osteoclast number in the cuboid (P &amp;lt; .01).<\/jats:p>\n               <jats:p>In the TNF-Tg model of chronic inflammatory arthritis, androgen is protective in erosive disease. The loss of endogenous androgen significantly accelerated the progression of inflammatory-erosive arthritis in male TNF-Tg mice to a similar severity as age-matched female mice. In addition, treatment with exogenous androgen prevented this observed bone loss in orchiectomized TNF-Tg males. Overall, androgen delays and limits bone erosion even in the presence of active inflammation and future studies are warranted to elucidate the associated mechanisms.<\/jats:p>","DOI":"10.1210\/jendso\/bvae169","type":"journal-article","created":{"date-parts":[[2024,10,1]],"date-time":"2024-10-01T18:23:58Z","timestamp":1727807038000},"source":"Crossref","is-referenced-by-count":5,"title":["Androgen Exhibits a Protective Role Against Focal Erosions in Murine TNF-induced Inflammatory Arthritis"],"prefix":"10.1210","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6691-5209","authenticated-orcid":false,"given":"Kiana","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Pathology & Laboratory Medicine, University of Rochester Medical Center , Rochester, NY 14642 ,","place":["USA"]},{"name":"Center for Musculoskeletal Research, University of Rochester Medical Center , Rochester, NY 14642 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University of Rochester Medical Center , Rochester, NY 14642 ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4028-7723","authenticated-orcid":false,"given":"Homaira","family":"Rahimi","sequence":"additional","affiliation":[{"name":"Center for Musculoskeletal Research, University of Rochester Medical Center , Rochester, NY 14642 ,","place":["USA"]},{"name":"Department of Pediatrics, University of Rochester Medical Center , Rochester, NY 14642 ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"80","published-online":{"date-parts":[[2024,10,1]]},"reference":[{"issue":"6","key":"2024102913421378300_bvae169-B1","doi-asserted-by":"crossref","first-page":"429","DOI":"10.1038\/nri2094","article-title":"Cytokines in the pathogenesis of rheumatoid arthritis","volume":"7","author":"McInnes","year":"2007","journal-title":"Nat Rev 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