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It has been recognized recently the association between metabolic syndrome and OA, particularly glucose metabolism in regulation of articular cartilage homeostasis and joint integrity. Whereas the role of glucose metabolism in subchondral bone sclerosis remains largely unknown during pathogenesis of OA. Consistent with common OA features, we observed subchondral bone sclerosis and abnormal bone remodeling in human OA joints and murine OA joints as reflected by hyperactive bone resorption and overall bone formation which was measured via dynamic histomorphometry. Osx-CreER;tdTomato mice also displayed the similar overall bone formation under injury-induced OA condition. Immunohistochemistry further revealed increased IL-1\u03b2 expression in human and murine OA subchondral bone. Given the inflammatory environment in joints under OA condition, we treated MC3T3-E1 cell, a pre-osteoblast cell line, with IL-1\u03b2 in this study and demonstrated that IL-1\u03b2 treatment could stimulate the cell osteogenic differentiation and meanwhile upregulate glycolysis and oxidative phosphorylation in cell cultures. More importantly, intraperitoneal injection of 2-deoxy-D-glucose (2-DG) and oligomycin (OGM), respectively, suppressed the subchondral bone glycolysis and oxidative phosphorylation in mice. Consequently, 2-DG and OGM treatment attenuated abnormal osteoblast differentiation and protected against aberrant bone formation in subchondral bone and articular cartilage degradation in wildtype mice following with joint injury. Collectively, these data strongly suggest glycolysis and oxidative may serve as important therapeutic targets for OA treatment.<\/jats:p>","DOI":"10.1093\/stmcls\/sxad012","type":"journal-article","created":{"date-parts":[[2023,1,27]],"date-time":"2023-01-27T01:49:41Z","timestamp":1674784181000},"page":"482-492","source":"Crossref","is-referenced-by-count":27,"title":["Inflammation-Mediated Aberrant Glucose Metabolism in Subchondral Bone Induces Osteoarthritis"],"prefix":"10.1093","volume":"41","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5289-489X","authenticated-orcid":false,"given":"Jun","family":"Ying","sequence":"first","affiliation":[{"name":"Department of Orthopaedic Surgery, The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Traditional Chinese Medicine) , Hangzhou , People\u2019s Republic of China"},{"name":"Institute of Orthopaedics and Traumatology, The First Affiliated Hospital of Zhejiang Chinese Medical University 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