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Here, we investigated whether D\u2010mannose interferes in chondrocyte ferroptotic cell death during osteoarthritic cartilage degeneration.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Materials and methods<\/jats:title>\n                    <jats:p>\n                      In vivo anterior cruciate ligament transection (ACLT)\u2010induced OA mouse model and an in vitro study of chondrocytes in an OA microenvironment induced by interleukin\u20101\u03b2 (IL\u20101\u03b2) exposure were employed. Combined with\n                      <jats:italic>Epas1<\/jats:italic>\n                      gene gain\u2010 and loss\u2010of\u2010function, histology, immunofluorescence, quantitative RT\u2010PCR, Western blot, cell viability and flow cytometry experiments were performed to evaluate the chondroprotective effects of D\u2010mannose in OA progression and the role of hypoxia\u2010inducible factor 2 alpha (HIF\u20102 \u03b1) in D\u2010mannose\u2010induced ferroptosis resistance of chondrocytes.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      D\u2010mannose exerted a chondroprotective effect by attenuating the sensitivity of chondrocytes to ferroptosis and alleviated OA progression. HIF\u20102\u03b1 was identified as a central mediator in D\u2010mannose\u2010induced ferroptosis resistance of chondrocytes. Furthermore, overexpression of HIF\u20102\u03b1 in chondrocytes by Ad\u2010\n                      <jats:italic>Epas1<\/jats:italic>\n                      intra\u2010articular injection abolished the chondroprotective effect of D\u2010mannose during OA progression and eliminated the role of D\u2010mannose as a ferroptosis suppressor.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>D\u2010mannose alleviates osteoarthritis progression by suppressing HIF\u20102\u03b1\u2010mediated chondrocyte sensitivity to ferroptosis, indicating D\u2010mannose to be a potential therapeutic strategy for ferroptosis\u2010related diseases.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/cpr.13134","type":"journal-article","created":{"date-parts":[[2021,9,25]],"date-time":"2021-09-25T03:42:27Z","timestamp":1632541347000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":171,"title":["D\u2010mannose alleviates osteoarthritis progression by inhibiting chondrocyte ferroptosis in a HIF\u20102\u03b1\u2010dependent manner"],"prefix":"10.1111","volume":"54","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3052-6703","authenticated-orcid":false,"given":"Xueman","family":"Zhou","sequence":"first","affiliation":[{"name":"State Key Laboratory of Oral Diseases and National Clinical Research Center for Oral Diseases Department of Orthodontics West China Hospital of Stomatology Sichuan University Chengdu China"},{"name":"Lab for Aging Research State Key Laboratory of Biotherapy and National Clinical Research Center for Geriatrics West China Hospital Sichuan University Chengdu 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