{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T16:32:25Z","timestamp":1787157145026,"version":"build-2736575974"},"reference-count":41,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T00:00:00Z","timestamp":1787097600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Animals"],"abstract":"<jats:p>Joint inflammation and extracellular matrix degradation are major contributors to the development of equine osteoarthritis and reduced athletic performance. Alpha-2-macroglobulin is a naturally occurring broad-spectrum inhibitor of proteases and inflammatory mediators that has emerged as a promising orthobiologic therapy. This study investigated the anti-inflammatory and matrix-protective effects of alpha-2-macroglobulin-enriched plasma in complementary in vitro and ex vivo equine models. Primary equine chondrocytes and synoviocytes isolated from healthy horses were stimulated with interleukin-1\u03b2 or lipopolysaccharide and treated with alpha-2-macroglobulin-enriched plasma or matched platelet-poor plasma. In parallel, an equine tendon explant model challenged with collagenase was used to evaluate extracellular matrix preservation. Alpha-2-macroglobulin-enriched plasma significantly reduced the production of tumor necrosis factor-\u03b1, interleukin-6, and matrix metalloproteinase-13, downregulated interleukin-1\u03b2 gene expression, and partially restored collagen type II expression in inflamed joint cells compared with platelet-poor plasma. In tendon explants, treatment preserved tissue architecture, reduced collagen degradation, and improved histological indices of matrix integrity under proteolytic challenge. These findings demonstrate that alpha-2-macroglobulin-enriched plasma exerts anti-inflammatory, anti-catabolic, and matrix-protective effects in experimental equine tissues. The results provide mechanistic support for the development of alpha-2-macroglobulin-based orthobiologic therapies as a complementary strategy for the management of synovitis and early osteoarthritis in horses.<\/jats:p>","DOI":"10.3390\/ani16162595","type":"journal-article","created":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T16:12:58Z","timestamp":1787155978000},"page":"2595","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Alpha-2-Macroglobulin-Enriched Plasma Modulates Inflammatory and Proteolytic Pathways in Experimental Equine Musculoskeletal Models"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6840-3154","authenticated-orcid":false,"given":"Enrico","family":"Gugliandolo","sequence":"first","affiliation":[{"name":"Department of Veterinary Sciences, University of Messina, 98168 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gianluca Antonio","family":"Franco","sequence":"additional","affiliation":[{"name":"Department of Veterinary Sciences, University of Messina, 98168 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8717-1966","authenticated-orcid":false,"given":"Vito","family":"Biondi","sequence":"additional","affiliation":[{"name":"Department of Veterinary Sciences, University of Messina, 98168 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-8461-7192","authenticated-orcid":false,"given":"Maria","family":"De Luca","sequence":"additional","affiliation":[{"name":"Department of Veterinary Sciences, University of Messina, 98168 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-7408-347X","authenticated-orcid":false,"given":"Yanne","family":"Van Reusel","sequence":"additional","affiliation":[{"name":"Department of Research and Development, INTIBIO, 3960 Bree, Belgium"},{"name":"Department of Morphology, Imaging, Orthopedics, Rehabilitation and Nutrition, Faculty of Veterinary Medicine, Ghent University, 9820 Merelbeke, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco","family":"Tosto","sequence":"additional","affiliation":[{"name":"Independent Researcher, 98166 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-4729-2322","authenticated-orcid":false,"given":"Francesca","family":"Inferrera","sequence":"additional","affiliation":[{"name":"Department CHIBIOFARAM, University of Messina, 98166 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4733-9573","authenticated-orcid":false,"given":"Giuseppe","family":"Catone","sequence":"additional","affiliation":[{"name":"Department of Veterinary Sciences, University of Messina, 98168 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0282-8966","authenticated-orcid":false,"given":"Jan H.","family":"Spaas","sequence":"additional","affiliation":[{"name":"Department of Research and Development, INTIBIO, 3960 Bree, Belgium"},{"name":"Department of Morphology, Imaging, Orthopedics, Rehabilitation and Nutrition, Faculty of Veterinary Medicine, Ghent University, 9820 Merelbeke, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"publisher","first-page":"5700","DOI":"10.1073\/pnas.82.17.5700","article-title":"Model of \u03b12-macroglobulin structure and function","volume":"82","author":"Feldman","year":"1985","journal-title":"Proc. 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