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Recent studies have found that chondrocytes can directly trans\u2010differentiate into osteoblasts in the process of endochondral bone formation, which indicates that cartilage formation and osteogenesis may be a continuous biological process. However, whether estrogen promotes the direct trans\u2010differentiation of chondrocytes into osteoblasts remains largely unknown. Chondrocytes were treated with different concentrations of 17\u03b2\u2010estradiol, and Alizarin Red staining and alkaline phosphatase activity assay were used to detected osteogenesis. Specific short hairpin RNA and tamoxifen were used to block the estrogen receptor (ER) pathway and osteogenic marker genes and downstream gene expression were detected using real\u2010time quantitative polymerase chain reaction, western blot, and immunohistochemistry staining. The findings showed that 17\u03b2\u2010estradiol promoted the chondrocyte osteogenesis in vitro, even at high concentrations. In addition, blocking of the ER\u03b1\/\u03b2 pathway inhibited the trans\u2010differentiation of chondrocytes into osteogenic cells. Furthermore, we found that dentin matrix protein 1 (DMP1), which is a direct downstream molecular of ER, was involved in 17\u03b2\u2010estradiol\/ER pathway\u2010regulated osteogenesis. As well, glycogen synthase kinase\u20103 beta (GSK\u20103\u03b2)\/\u03b2\u2010catenin signal pathway also participates in ER\u03b1\/\u03b2\/DMP1\u2010regulated chondrocyte osteogenesis. The GSK\u20103\u03b2\/\u03b2\u2010catenin signal pathway was involved in ER\u03b1\/\u03b2\/DMP1\u2010regulated chondrocyte osteogenesis. These findings suggest that ER\/DMP1\/GSK\u20103\u03b2\/\u03b2\u2010catenin plays a vital role in estrogen regulation of chondrocyte osteogenesis and provide a therapeutic target for short stature caused by epiphyseal fusion.<\/jats:p>","DOI":"10.1111\/joa.13612","type":"journal-article","created":{"date-parts":[[2022,1,26]],"date-time":"2022-01-26T17:39:44Z","timestamp":1643218784000},"page":"1152-1161","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["ER\u03b1\/\u03b2\/DMP1 axis promotes trans\u2010differentiation of chondrocytes to bone cells through GSK\u20103\u03b2\/\u03b2\u2010catenin pathway"],"prefix":"10.1111","volume":"240","author":[{"given":"Xue","family":"Yan","sequence":"first","affiliation":[{"name":"Department of Pediatrics The Second Hospital of Hebei Medical University  Shijiazhuang 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