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Here, we reveal that the CXCR2 ligand granulocyte chemotactic protein 2 (GCP\u20102) was expressed, during embryonic development, within the prospective permanent articular cartilage, but not in the epiphyseal cartilage destined to be replaced by bone. GCP\u20102 expression was retained in adult articular cartilage. GCP\u20102 loss\u2010of\u2010function inhibited extracellular matrix production. GCP\u20102 treatment promoted chondrogenesis\n                    <jats:italic>in\u00a0vitro<\/jats:italic>\n                    and in human cartilage organoids implanted in nude mice\n                    <jats:italic>in\u00a0vivo<\/jats:italic>\n                    . To exploit the chondrogenic activity of GCP\u20102, we disrupted its chemotactic activity, by mutagenizing a glycosaminoglycan binding sequence, which we hypothesized to be required for the formation of a GCP\u20102 haptotactic gradient on endothelia. This mutated version (GCP\u20102\u2010T) had reduced capacity to induce transendothelial migration\n                    <jats:italic>in\u00a0vitro<\/jats:italic>\n                    and\n                    <jats:italic>in\u00a0vivo<\/jats:italic>\n                    , without affecting downstream receptor signaling through AKT, and chondrogenic activity. Intra\u2010articular adenoviral overexpression of GCP\u20102\u2010T, but not wild\u2010type GCP\u20102, reduced pain and cartilage loss in instability\u2010induced osteoarthritis in mice. We suggest that GCP\u20102\u2010T may be used for disease modification in osteoarthritis.\n                  <\/jats:p>","DOI":"10.15252\/emmm.202216218","type":"journal-article","created":{"date-parts":[[2022,12,12]],"date-time":"2022-12-12T03:31:29Z","timestamp":1670815889000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Disease modification and symptom relief in osteoarthritis using a mutated GCP\u20102\/CXCL6 chemokine"],"prefix":"10.1038","volume":"15","author":[{"given":"Sara","family":"Caxaria","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0425-1141","authenticated-orcid":false,"given":"Nikolaos","family":"Kouvatsos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suzanne 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