KDM6B Regulates BMP2 to Promote Osteoblast Differentiation and Ameliorates Alcohol-Induced Osteoporosis

Alcohol-induced osteoporosis (AOP) is a condition characterized by decreased bone mass and increased fracture risk due to excessive alcohol consumption. This study aimed to investigate the impact of ethanol on osteogenic differentiation through the KDM6B/BMP2 axis in AOP pathogenesis. Bone marrow mesenchymal stem cells (BMSCs) were cultured and exposed to ethanol to simulate AOP conditions. The expression levels of KDM6B, BMP2, and osteogenic markers were evaluated using RT-PCR, Western blotting, and immunohistochemistry. Osteogenic differentiation was assessed through alkaline phosphatase (ALP) activity assay and Alizarin Red staining experiment. The regulatory role of KDM6B in BMP2 demethylation was investigated using Chromatin Immunoprecipitation (ChIP) assay for H3K27me3 methylation levels. KDM6B and BMP2 expression was found decreased in AOP bone samples, and a positive correlation between KDM6B and BMP2 expression was observed. Ethanol treatment resulted in the downregulation of KDM6B, BMP2, and osteogenic markers in BMSCs, while upregulation of KDM6B rescued these phenomena. Moreover, ethanol treatment elevated the H3K27me3 methylation level of BMP2 promotor region, which was also reversed by KDM6B upregulation. Meanwhile, downregulation of BMP2 reversed the pro-osteogenic effects of KDM6B upregulation. KDM6B inhibits the H3K27me3 methylation of BMP2 to promote osteoblast differentiation and therefore ameliorates alcohol-induced osteoporosis.