{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T12:57:28Z","timestamp":1790168248790,"version":"4.1.0"},"reference-count":50,"publisher":"BMJ","issue":"1","license":[{"start":{"date-parts":[[2023,2,21]],"date-time":"2023-02-21T00:00:00Z","timestamp":1676937600000},"content-version":"unspecified","delay-in-days":20,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["RMD Open"],"accepted":{"date-parts":[[2023,1,18]]},"published-print":{"date-parts":[[2023,2]]},"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Low-grade inflammation plays a pivotal role in osteoarthritis (OA) through exposure to reactive oxygen species (ROS). In chondrocytes, NADPH oxidase 4 (NOX4) is one of the major ROS producers. In this study, we evaluated the role of NOX4 on joint homoeostasis after destabilisation of the medial meniscus (DMM) in mice.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Experimental OA was simulated on cartilage explants using interleukin-1\u03b2 (IL-1\u03b2) and induced by DMM in wild-type (WT) and NOX4 knockout (NOX4\n                      <jats:sup>-\/-<\/jats:sup>\n                      ) mice. We evaluated NOX4 expression, inflammation, cartilage metabolism and oxidative stress by immunohistochemistry. Bone phenotype was also determined by micro-CT and histomorphometry.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Whole body NOX4 deletion attenuated experimental OA in mice, with a significant reduction of the OARSI score at 8 weeks. DMM increased total subchondral bone plate (SB.Th), epiphysial trabecular thicknesses (Tb.Th) and bone volume fraction (BV\/TV) in both NOX4\n                      <jats:sup>-\/-<\/jats:sup>\n                      and wild-type (WT) mice. Interestingly, DDM decreased total connectivity density (Conn.Dens) and increased medial BV\/TV and Tb.Th only in WT mice. Ex vivo, NOX4 deficiency increased aggrecan (AGG) expression and decreased matrix metalloproteinase 13 (MMP13) and collagen type I (COL1) expression. IL-1\u03b2 increased NOX4 and 8-hydroxy-2'-deoxyguanosine (8-OHdG) expression in WT cartilage explants but not in NOX4\n                      <jats:sup>-\/-<\/jats:sup>\n                      . In vivo, absence of NOX4 increased anabolism and decreased catabolism after DMM. Finally, NOX4 deletion decreased synovitis score, 8-OHdG and F4\/80 staining following DMM.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>NOX4 deficiency restores cartilage homoeostasis, inhibits oxidative stress, inflammation and delays OA progression after DMM in mice. These findings suggest that NOX4 represent a potential target to counteract for OA treatment.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/rmdopen-2022-002856","type":"journal-article","created":{"date-parts":[[2023,2,21]],"date-time":"2023-02-21T09:41:50Z","timestamp":1676972510000},"page":"e002856","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":19,"title":["NADPH oxidase 4 deficiency attenuates experimental osteoarthritis in mice"],"prefix":"10.1136","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5712-582X","authenticated-orcid":false,"given":"F\u00e9lix","family":"Renaudin","sequence":"first","affiliation":[{"name":"Department of Cell Physiology and Metabolism, Universit\u00e9 de Gen\u00e8ve Facult\u00e9 de m\u00e9decine, Geneve, Switzerland"},{"name":"Department of Orthopaedic Surgery, Geneva University Hospitals, Geneve, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karim","family":"Oudina","sequence":"additional","affiliation":[{"name":"Department of Cell Physiology and Metabolism, Universit\u00e9 de Gen\u00e8ve Facult\u00e9 de m\u00e9decine, Geneve, Switzerland"},{"name":"Department of Orthopaedic Surgery, Geneva University Hospitals, Geneve, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maude","family":"Gerbaix","sequence":"additional","affiliation":[{"name":"Service of Bone Diseases, Department of Medicine, Geneva University Hospitals, Geneve, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manon","family":"McGilligan Subilia","sequence":"additional","affiliation":[{"name":"Department of Cell Physiology and Metabolism, Universit\u00e9 de Gen\u00e8ve Facult\u00e9 de m\u00e9decine, Geneve, Switzerland"},{"name":"Department of Orthopaedic Surgery, Geneva University Hospitals, Geneve, 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