{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T18:41:01Z","timestamp":1788892861620,"version":"build-2803163510"},"reference-count":49,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2025,11,23]],"date-time":"2025-11-23T00:00:00Z","timestamp":1763856000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,11,23]],"date-time":"2025-11-23T00:00:00Z","timestamp":1763856000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100004895","name":"European Social Fund Plus","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004895","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100008977","name":"Universit\u00e4t Ulm","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100008977","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["MedComm"],"published-print":{"date-parts":[[2025,12]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Posttraumatic osteoarthritis (PTOA) is a special form of osteoarthritis (OA), developing after joint injuries. Except for some minor clinical differences, no biologic marker has yet been identified to distinguish idiopathic OA (IOA) from PTOA. In this study, we investigated the expression of the stress\u2010responsive cytokine growth differentiation factor 15 (GDF\u201015) in clinical samples from the Ulm OA study cohort and in a human ex vivo cartilage trauma model. GDF\u201015 levels were significantly higher in synovial fluid of PTOA patients as compared to IOA patients. We confirmed that fibroblast\u2010like synoviocytes secreted GDF\u201015 after stimulation with medium of ex vivo\u2010traumatized cartilage. Moreover, GDF\u201015 and its receptor, GFRAL, were elevated in highly degenerated OA cartilage. By means of a human cartilage trauma model, we discovered that chondrocytes produced GDF\u201015 upon tissue injury, while antioxidative treatment attenuated GDF\u201015 secretion. In fact, GDF\u201015 expression was mediated by oxidative stress and subsequent activation of p53. As a transcriptional target of p53, GDF\u201015 was associated with chondrosenescence. However, GDF\u201015 induced pro\u2010regenerative response in chondrocytes, characterized by enhanced proliferation as well as chondro\u2010 and cell protection after cartilage trauma. Overall, this study first describes GDF\u201015 as a senescence\u2010associated but potentially pro\u2010regenerative cytokine in the context of human PTOA.<\/jats:p>","DOI":"10.1002\/mco2.70484","type":"journal-article","created":{"date-parts":[[2025,11,23]],"date-time":"2025-11-23T15:42:01Z","timestamp":1763912521000},"source":"Crossref","is-referenced-by-count":1,"title":["Growth\/Differentiation Factor 15 Promotes a Pro\u2010Regenerative Response in Chondrocytes Upon Cartilage Injury"],"prefix":"10.1002","volume":"6","author":[{"given":"Sara Sofi","family":"Marques","sequence":"first","affiliation":[{"name":"Department of Orthopedics Division for Biochemistry of Joint and Connective Tissue Diseases University of Ulm  Ulm Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandra","family":"Liebaug","sequence":"additional","affiliation":[{"name":"Department of Orthopedics Division for Biochemistry of Joint and Connective Tissue Diseases University of Ulm  Ulm Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Svenja","family":"Maurer","sequence":"additional","affiliation":[{"name":"Department of Orthopedics Division for Biochemistry of Joint and Connective Tissue Diseases University of Ulm  Ulm Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dietrich","family":"Rothenbacher","sequence":"additional","affiliation":[{"name":"Institute of Epidemiology and Medical Biometry Ulm University  Ulm Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rolf E.","family":"Brenner","sequence":"additional","affiliation":[{"name":"Department of Orthopedics Division for Biochemistry of Joint and Connective Tissue Diseases University of Ulm  Ulm Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0048-5047","authenticated-orcid":false,"given":"Jana","family":"Riegger","sequence":"additional","affiliation":[{"name":"Department of Orthopedics 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