{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T17:00:36Z","timestamp":1780592436728,"version":"3.54.1"},"reference-count":17,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2022,2,22]],"date-time":"2022-02-22T00:00:00Z","timestamp":1645488000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000069","name":"National Institute of Arthritis and Musculoskeletal and Skin Diseases","doi-asserted-by":"publisher","award":["AR050938"],"award-info":[{"award-number":["AR050938"]}],"id":[{"id":"10.13039\/100000069","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["AG044034"],"award-info":[{"award-number":["AG044034"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["OD011118"],"award-info":[{"award-number":["OD011118"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["acrjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["ACR Open Rheumatology"],"published-print":{"date-parts":[[2022,5]]},"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>The study objective was to determine whether overexpression of the mitochondrial antioxidant peroxidase, peroxiredoxin 3 (Prx3), reduces the severity of osteoarthritis (OA) in mice.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Age\u2010related OA (age 18 and 24 months) and OA induced by destabilization of the medial meniscus (DMM at age 6 months) were assessed in male mice that overexpress a human <jats:italic>Prdx3<\/jats:italic> transgene encoding the Prx3 protein. Lox\u2010stop\u2010lox\u2010Prdx3 (iPrdx3) mice were crossed with aggrecan\u2010Cre<jats:sup>ERT2<\/jats:sup> mice to produce iPrdx3AgCre<jats:sup>ERT2<\/jats:sup> or with Col2Cre to produce iPrdx3Col2Cre mice. Germline transgenics (Prdx3Tg) were also evaluated. Prx3 protein level was assessed by immunoblotting and functionally after induction of elevated mitochondrial hydrogen peroxide (H<jats:sub>2<\/jats:sub>O<jats:sub>2<\/jats:sub>) using menadione. Histological sections of stifle joints were scored for cartilage damage (Articular Cartilage Structure score [ACS]), osteophytes, and synovial hyperplasia and were evaluated by histomorphometry.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Overexpression of Prx3 maintained mitochondrial membrane integrity and inhibited p38 phosphorylation in the presence of elevated H<jats:sub>2<\/jats:sub>O<jats:sub>2<\/jats:sub>. ACS scores of 18\u2010month\u2010old iPrdx3AgCre<jats:sup>ERT2<\/jats:sup> mice (mean \u00b1 SD, 4.88 \u00b1\u20095.05) were significantly lower than age\u2010matched iPrdx3 controls (11.75 \u00b1\u20096.34, <jats:italic>P<\/jats:italic> =\u20090.002) and trended lower in the 18\u2010month Prdx3Tg group (<jats:italic>P<\/jats:italic> =\u20090.14), whereas no significant differences between experimental and control groups at 24 months of age or in OA induced by DMM surgery were noted. Osteophyte scores trended lower in the 18\u2010month\u2010old Prdx3Tg group (<jats:italic>P<\/jats:italic> =\u20090.09) and at 24 months in the iPrdx3Col2Cre mice (<jats:italic>P<\/jats:italic> =\u20090.05). There were no significant group differences in synovial hyperplasia or histomorphometric measures.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Overexpression of the mitochondrial peroxidase Prx3 reduced the severity of age\u2010related OA, but not at advanced ages and not in DMM\u2010induced OA in younger mice.<\/jats:p><\/jats:sec>","DOI":"10.1002\/acr2.11420","type":"journal-article","created":{"date-parts":[[2022,2,22]],"date-time":"2022-02-22T03:03:35Z","timestamp":1645499015000},"page":"441-446","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Overexpression of Peroxiredoxin 3 in Cartilage Reduces the Severity of <scp>Age\u2010Related<\/scp> Osteoarthritis But Not Surgically Induced Osteoarthritis in Mice"],"prefix":"10.1002","volume":"4","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2832-6144","authenticated-orcid":false,"given":"Richard F.","family":"Loeser","sequence":"first","affiliation":[{"name":"University of North Carolina School of Medicine  Chapel Hill"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philip R.","family":"Coryell","sequence":"additional","affiliation":[{"name":"University of North Carolina School of Medicine  Chapel Hill"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandra R.","family":"Armstrong","sequence":"additional","affiliation":[{"name":"University of Minnesota College of Veterinary Medicine  St. Paul"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John A.","family":"Collins","sequence":"additional","affiliation":[{"name":"University of North Carolina School of Medicine  Chapel Hill"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Priya","family":"Gopalakrishnan","sequence":"additional","affiliation":[{"name":"University of North Carolina School of Medicine  Chapel 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