{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,8]],"date-time":"2026-05-08T17:16:30Z","timestamp":1778260590621,"version":"3.51.4"},"reference-count":24,"publisher":"Public Library of Science (PLoS)","issue":"3","license":[{"start":{"date-parts":[[2021,3,2]],"date-time":"2021-03-02T00:00:00Z","timestamp":1614643200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/publicdomain\/zero\/1.0\/"}],"funder":[{"name":"DOD Peer Reviewed Medical Research Program (PRMRP) Discovery Award","award":["W81XWH-15-1-0231"],"award-info":[{"award-number":["W81XWH-15-1-0231"]}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p>The expression of some chemokines and chemokine receptors is induced during the development of post-traumatic osteoarthritis (PTOA), but their involvement in the pathogenesis of the disease is unclear. The goal of this study was to test whether CCL21 and CXCL13 play a role in PTOA development. For this purpose, we evaluated the expression profiles of the chemokines<jats:italic>Ccl21<\/jats:italic>and<jats:italic>Cxcl13<\/jats:italic>, matrix metalloproteinase enzymes<jats:italic>Mmp3<\/jats:italic>and<jats:italic>Mmp13<\/jats:italic>, and inflammatory cell markers in response to partial medial meniscectomy and destabilization (MMD). We then assessed the effect of local administration of CCL21 neutralizing antibody on PTOA development and post-knee injury inflammation. The mRNA expression of both<jats:italic>Ccl21<\/jats:italic>and<jats:italic>Cxcl13<\/jats:italic>was induced early post-surgery, but only<jats:italic>Ccl21<\/jats:italic>mRNA levels remained elevated 4 weeks post-surgery in rat MMD-operated knees compared to controls. This suggests that while both CXCL13 and CCL21 are involved in post-surgery inflammation, CCL21 is necessary for development of PTOA. A significant increase in the mRNA levels of<jats:italic>Cd4<\/jats:italic>,<jats:italic>Cd8<\/jats:italic>and<jats:italic>Cd20<\/jats:italic>was observed during the first 3 days post-surgery. Significantly, treatment with CCL21 antibody reduced post-surgical inflammation that was accompanied by a reduction in the expression of<jats:italic>Mmp3<\/jats:italic>and<jats:italic>Mmp13<\/jats:italic>and post-MMD cartilage degradation. Our findings are consistent with a role for CCL21 in mediating changes in early inflammation and subsequent cartilage degeneration in response to knee injury. Our results suggest that targeting CCL21 signaling pathways may yield new therapeutic approaches effective in delaying or preventing PTOA development following injury.<\/jats:p>","DOI":"10.1371\/journal.pone.0247913","type":"journal-article","created":{"date-parts":[[2021,3,2]],"date-time":"2021-03-02T18:47:28Z","timestamp":1614710848000},"page":"e0247913","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":8,"title":["Evaluation of CCL21 role in post-knee injury inflammation and early cartilage degeneration"],"prefix":"10.1371","volume":"16","author":[{"given":"Mohan","family":"Subburaman","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6407-9411","authenticated-orcid":true,"given":"Bouchra","family":"Edderkaoui","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2021,3,2]]},"reference":[{"issue":"10","key":"pone.0247913.ref001","doi-asserted-by":"crossref","first-page":"1756e69","DOI":"10.1177\/0363546507307396","article-title":"The long-term consequence of anterior cruciate ligament and meniscus injuries: osteoarthritis.","volume":"35","author":"LS Lohmander","year":"2007","journal-title":"Am J Sports Med."},{"issue":"10","key":"pone.0247913.ref002","doi-asserted-by":"crossref","first-page":"739","DOI":"10.1097\/01.bot.0000246468.80635.ef","article-title":"Posttraumatic osteoarthritis: a first estimate of incidence, prevalence, and burden of disease.","volume":"20","author":"TD Brown","year":"2006","journal-title":"J Orthop Trauma."},{"issue":"3","key":"pone.0247913.ref003","doi-asserted-by":"crossref","first-page":"705","DOI":"10.1002\/art.33388","article-title":"Microarray analysis reveals age-related differences in gene expression during the development of osteoarthritis in mice","volume":"64","author":"RF Loeser","year":"2012","journal-title":"Arthritis Rheum"},{"issue":"1","key":"pone.0247913.ref004","doi-asserted-by":"crossref","first-page":"e54633","DOI":"10.1371\/journal.pone.0054633","article-title":"Disease progression and phasic changes in gene expression in a mouse model of osteoarthritis","volume":"8","author":"RF Loeser","year":"2013","journal-title":"PLoS One"},{"key":"pone.0247913.ref005","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1016\/j.gene.2014.03.022","article-title":"Integration of gene expression data with network based analysis to identify signaling and metabolic pathways regulated during the development of osteoarthritis","volume":"542","author":"AL Olex","year":"2014","journal-title":"Gene"},{"key":"pone.0247913.ref006","doi-asserted-by":"crossref","first-page":"914","DOI":"10.1002\/art.30232","article-title":"2nd, Shahrara S. 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