{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T00:48:04Z","timestamp":1786668484838,"version":"build-2736575974"},"reference-count":68,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2025,9,1]],"date-time":"2025-09-01T00:00:00Z","timestamp":1756684800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Town &amp; Country Farms in Lexington, KY"},{"name":"Osteoarthritis Alliance of Kentucky"},{"name":"Early Career Award the Grayson-Jockey Club Research Foundation"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Synovitis resolution is critical for joint homeostasis and prevents the progression of osteoarthritis (OA). Treatments like NSAIDs and intra-articular corticosteroids relieve symptoms by blocking pro-inflammatory mediators, but also impair the production of pro-resolving mediators, contributing to the likelihood of chronic synovitis. PPAR\u03b3 signaling is an essential mechanism of synovitis resolution, which is decreased in OA tissues. To evaluate the potential of PPAR\u03b3 agonists to promote pro-resolving pathways, equine macrophages cultured in autologous, normal, or inflamed synovial fluid (n = 10 horses) were treated with pioglitazone, geraniol, or both. Treatments modulated patterns of gene expression, increasing the expression of early drivers of resolution RELB and IL6, followed by increased NRF2 and PPARGC1A expression. Concentrations of TNF-\u03b1 in conditioned synovial fluid significantly decreased as an early response to treatment, while IL10 concentrations also declined over time, suggesting increased tolerance to inflammatory stimuli and decreased compensatory feedback. Using an equine model of synovitis, intra-articular delivery of pioglitazone (n = 3 horses) or geraniol (n = 4 horses) was associated with decreased markers of synovium inflammation (geraniol) and enhanced cartilage proteoglycan preservation (geraniol and pioglitazone). In this small cohort of horses, no systemic or articular side effects were observed. Further studies optimizing treatment doses and regimens for intra-articular PPAR\u03b3 agonism as a pro-resolving OA therapy are warranted.<\/jats:p>","DOI":"10.3390\/biom15091267","type":"journal-article","created":{"date-parts":[[2025,9,1]],"date-time":"2025-09-01T13:27:44Z","timestamp":1756733264000},"page":"1267","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["PPAR\u03b3 Agonism Modulates Synovial Macrophage and Cartilage Responses in an Equine Model of Synovial Inflammation\u2014Implications for Joint Therapy"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-6875-4055","authenticated-orcid":false,"given":"Sl\u00e0ine F.","family":"Chaimbeul","sequence":"first","affiliation":[{"name":"Department of Veterinary Clinical Sciences, University of Copenhagen, 2630 Taastrup, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5156-8128","authenticated-orcid":false,"given":"Nubia N. P.","family":"Rodrigues","sequence":"additional","affiliation":[{"name":"Faculdade de Medicina Veterin\u00e1ria e Zootecnia, Universidade S\u00e3o Paulo, S\u00e3o Paulo 05508-270, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-7720-3617","authenticated-orcid":false,"given":"Danny D.","family":"Thurston","sequence":"additional","affiliation":[{"name":"Rood and Riddle Equine Hospital, Saratoga, NY 12866, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1348-641X","authenticated-orcid":false,"given":"Kirsten E.","family":"Scoggin","sequence":"additional","affiliation":[{"name":"Gluck Equine Research Center, Department of Veterinary Sciences, University of Kentucky, Lexington, KY 40506, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer","family":"Janes","sequence":"additional","affiliation":[{"name":"Veterinary Diagnostic Laboratory, Department of Veterinary Sciences, University of Kentucky, Lexington, KY 40506, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cale A.","family":"Jacobs","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Surgery, College of Medicine, Harvard University, Boston, MA 02138, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James N.","family":"MacLeod","sequence":"additional","affiliation":[{"name":"Gluck Equine Research Center, Department of Veterinary Sciences, University of Kentucky, Lexington, KY 40506, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Austin V.","family":"Stone","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Surgery, College of Medicine, University of Kentucky, Lexington, KY 40506, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1829-4978","authenticated-orcid":false,"given":"Bruno C.","family":"Menarim","sequence":"additional","affiliation":[{"name":"Gluck Equine Research Center, Department of Veterinary Sciences, University of Kentucky, Lexington, KY 40506, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,9,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"527","DOI":"10.15585\/mmwr.mm6620a2","article-title":"Prevalence of Arthritis and Arthritis-Attributable Activity Limitation by Urban-Rural County Classification-United States, 2015","volume":"66","author":"Boring","year":"2017","journal-title":"MMWR Morb. 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