{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T13:08:06Z","timestamp":1791378486203,"version":"4.3.2"},"reference-count":59,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2022,2,14]],"date-time":"2022-02-14T00:00:00Z","timestamp":1644796800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Osteoarthritis (OA) is a whole joint disease characterized by an important remodeling of the osteochondral junction. It includes cartilage mineralization due to chondrocyte hypertrophic differentiation and bone sclerosis. Here, we investigated whether gremlin-1 (Grem-1) and its BMP partners could be involved in the remodeling events of the osteochondral junction in OA. We found that Grem-1, BMP-2, and BMP-4 immunostaining was detected in chondrocytes from the deep layer of cartilage and in subchondral bone of knee OA patients, and was positively correlated with cartilage damage. ELISA assays showed that bone released more Grem-1 and BMP-4 than cartilage, which released more BMP-2. In vitro experiments evidenced that compression stimulated the expression and the release of Grem-1 and BMP-4 by osteoblasts. Grem-1 was also overexpressed during the prehypertrophic to hypertrophic differentiation of murine articular chondrocytes. Recombinant Grem-1 stimulated Mmp-3 and Mmp-13 expression in murine chondrocytes and osteoblasts, whereas recombinant BMP-4 stimulated the expression of genes associated with angiogenesis (Angptl4 and osteoclastogenesis (Rankl and Ccl2). In conclusion, Grem-1 and BMP-4, whose expression at the osteochondral junction increased with OA progression, may favor the pathological remodeling of the osteochondral junction by inducing a catabolic and tissue remodeling program in hypertrophic chondrocytes and osteoblasts.<\/jats:p>","DOI":"10.3390\/ijms23042084","type":"journal-article","created":{"date-parts":[[2022,2,14]],"date-time":"2022-02-14T20:26:42Z","timestamp":1644870402000},"page":"2084","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Gremlin-1 and BMP-4 Overexpressed in Osteoarthritis Drive an Osteochondral-Remodeling Program in Osteoblasts and Hypertrophic Chondrocytes"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6473-3823","authenticated-orcid":false,"given":"Maria-Luisa","family":"P\u00e9rez-Lozano","sequence":"first","affiliation":[{"name":"Centre de Recherche Saint-Antoine (CRSA), INSERM, Sorbonne Universit\u00e9, F-75012 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laure","family":"Sudre","sequence":"additional","affiliation":[{"name":"Centre de Recherche Saint-Antoine (CRSA), INSERM, Sorbonne Universit\u00e9, F-75012 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandy","family":"van Eegher","sequence":"additional","affiliation":[{"name":"Centre de Recherche Saint-Antoine (CRSA), INSERM, Sorbonne Universit\u00e9, F-75012 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dani\u00e8le","family":"Citadelle","sequence":"additional","affiliation":[{"name":"Centre de Recherche Saint-Antoine (CRSA), INSERM, Sorbonne Universit\u00e9, F-75012 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Audrey","family":"Pigenet","sequence":"additional","affiliation":[{"name":"Centre de Recherche Saint-Antoine (CRSA), INSERM, Sorbonne Universit\u00e9, F-75012 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie-Hel\u00e8ne","family":"Lafage-Proust","sequence":"additional","affiliation":[{"name":"Facult\u00e9 de M\u00e9decine, INSERM U1059, Universit\u00e9 Jean Monnet, F-42270 Saint-Priest en Jarez, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0048-897X","authenticated-orcid":false,"given":"Philippe","family":"Pastoureau","sequence":"additional","affiliation":[{"name":"Immuno-Inflammatory Diseases Department, Servier Research Institute, F-92150 Suresnes, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fr\u00e9d\u00e9ric","family":"De Ceuninck","sequence":"additional","affiliation":[{"name":"Immuno-Inflammatory Diseases Department, Servier Research Institute, F-92150 Suresnes, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francis","family":"Berenbaum","sequence":"additional","affiliation":[{"name":"Centre de Recherche Saint-Antoine (CRSA), INSERM, Sorbonne Universit\u00e9, F-75012 Paris, France"},{"name":"Centre de Recherche Saint-Antoine (CRSA), INSERM, Sorbonne Universit\u00e9, AP-HP H\u00f4pital Saint Antoine, F-75012 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xavier","family":"Houard","sequence":"additional","affiliation":[{"name":"Centre de Recherche Saint-Antoine (CRSA), INSERM, Sorbonne Universit\u00e9, F-75012 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,2,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1697","DOI":"10.1002\/art.34453","article-title":"Osteoarthritis: A disease of the joint as an organ","volume":"64","author":"Loeser","year":"2012","journal-title":"Arthritis Rheum."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"437","DOI":"10.1038\/nrrheum.2014.44","article-title":"The individual and socioeconomic impact of osteoarthritis","volume":"10","author":"Hunter","year":"2014","journal-title":"Nat. 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