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formation, particularly increased osteoclastogenesis. However, the mechanisms by which epigenetic factors regulate osteoclast precursor differentiation during osteoclastogenesis remain poorly understood. Here, we show that the specific knockout of the chromatin remodeling factor Arid1a in bone marrow\u2013derived macrophages (BMDMs) results in increased bone mass. The loss of Arid1a in BMDM inhibits cell\u2013cell fusion and maturation of osteoclast precursors, thereby suppressing osteoclast differentiation. Mechanistically, Arid1a increases the chromatin access in the gene promoter region of sialic acid\u2013binding Ig-like lectin 15 (Siglec15) by transcription factor Jun\/Fos, which results in the upregulation of Siglec15 and promotion of osteoclast differentiation. However, the loss of Arid1a reprograms the chromatin structure to restrict Siglec15 expression in osteoclast precursors, thereby inhibiting BMDM differentiation into mature osteoclasts. Deleting Arid1a after ovariectomy (a model for postmenopausal bone loss) alleviated bone loss and maintained bone mass. In summary, epigenetic reprogramming mediated by Arid1a loss suppresses osteoclast differentiation and may serve as a promising therapeutic strategy for treating bone loss diseases.<\/jats:p>","DOI":"10.1093\/jbmr\/zjae042","type":"journal-article","created":{"date-parts":[[2024,3,11]],"date-time":"2024-03-11T17:25:36Z","timestamp":1710177936000},"page":"775-790","source":"Crossref","is-referenced-by-count":12,"title":["The chromatin remodeling factor Arid1a cooperates with Jun\/Fos to promote osteoclastogenesis by epigenetically upregulating <i>Siglec15<\/i> expression"],"prefix":"10.1093","volume":"39","author":[{"given":"Yongxing","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Orthopedics, The Second Affiliated Hospital Zhejiang University School of Medicine , Hangzhou, Zhejiang 310009 , PR China"},{"name":"Orthopedics Research Institute of Zhejiang University , Hangzhou, Zhejiang 310009 , PR China"},{"name":"Key Laboratory of Motor System Disease Research 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