{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T15:40:02Z","timestamp":1787240402199,"version":"build-2736575974"},"reference-count":120,"publisher":"American Veterinary Medical Association (AVMA)","issue":"2","license":[{"start":{"date-parts":[[2026,2,1]],"date-time":"2026-02-01T00:00:00Z","timestamp":1769904000000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["ajvr"],"published-print":{"date-parts":[[2026,2,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Orthobiologics rich in alpha-2-macroglobulin (A2M) are being used with increasing frequency to treat equine and human osteoarthritis (OA). The glycoprotein is concentrated from whole blood, typically prepared by a commercial device, and is administered IA with the goal of ameliorating inflammation and associated pain. In recent years, numerous investigations have elucidated A2M\u2019s mechanism of action and its effects on joint cells; however, none have used the horse as a model nor have they investigated the commercially available kit for equine orthobiologic preparation, Alpha2EQ. This narrative review presents the most pertinent work on A2M, which supports its current clinical use as an OA treatment. Alpha-2-macroglobulin has been studied in a variety of preclinical models, in vivo, and in clinical patients. As a naturally occurring and potent protease inhibitor, A2M acts to regulate key components of the OA inflammatory cascade, from cytokines and chemokines, which propagate synovitis, to disintegrins and metalloproteinases that degrade the cartilage extracellular matrix. Three main mechanisms of action contribute to A2M\u2019s modulation of joint inflammation and concomitant OA progression across species: the bait-and-trap mechanism, direct binding interactions, and regulation of gene expression. In vivo, A2M treatment results in improved histopathology scores, gait improvement in animals, and improved patient-reported outcomes in people. Though substantial evidence exists for A2M\u2019s anti-inflammatory effects and role in OA treatment, further studies will be required to elucidate the mechanisms of the equine orthobiologic.<\/jats:p>","DOI":"10.2460\/ajvr.25.09.0318","type":"journal-article","created":{"date-parts":[[2025,10,31]],"date-time":"2025-10-31T13:38:22Z","timestamp":1761917902000},"source":"Crossref","is-referenced-by-count":2,"title":["Evidence for alpha-2-macroglobulin as an orthobiologic osteoarthritis therapy: a narrative review"],"prefix":"10.2460","volume":"87","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1636-2439","authenticated-orcid":true,"given":"Brenna R.","family":"Pugliese","sequence":"first","affiliation":[{"name":"Department of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC"},{"name":"Comparative Medicine Institute, North Carolina State University, Raleigh, NC"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1993-8141","authenticated-orcid":true,"given":"Lauren V.","family":"Schnabel","sequence":"additional","affiliation":[{"name":"Department of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC"},{"name":"Comparative Medicine Institute, North Carolina State University, Raleigh, NC"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1272","reference":[{"issue":"9","key":"B1","series-title":"Lancet Rheumatol","first-page":"e508","article-title":"Global, regional, and national burden of osteoarthritis, 1990\u20132020 and projections to 2050: a systematic analysis for the Global Burden of Disease Study 2021","author":"Steinmetz JD","year":"2023","unstructured":"Steinmetz JD, Culbreth GT, Haile LM, et al. Global, regional, and national burden of osteoarthritis, 1990\u20132020 and projections to 2050: a systematic analysis for the Global Burden of Disease Study 2021. Lancet Rheumatol. 2023;5(9):e508\u2013e522. doi:10.1016\/s2665-9913(23)00163-7"},{"key":"B2","series-title":"Vet J","first-page":"106132","article-title":"Prevalence of osteoarthritis in the shoulder, elbow, hip and stifle joints of dogs older than 8 years","author":"Roitner M","year":"2024","unstructured":"Roitner M, Klever J, Reese S, Meyer-Lindenberg A. Prevalence of osteoarthritis in the shoulder, elbow, hip and stifle joints of dogs older than 8 years. Vet J. 2024;305:106132. doi:10.1016\/j.tvjl.2024.106132"},{"issue":"11","key":"B3","series-title":"Bone Jt Res","first-page":"297","article-title":"The horse as a model of naturally occurring osteoarthritis","author":"McIlwraith CW","year":"2012","unstructured":"McIlwraith CW, Frisbie DD, Kawcak CE. The horse as a model of naturally occurring osteoarthritis. 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