细胞生物学
基因敲除
组蛋白
化学
下调和上调
小RNA
甲基转移酶
表观遗传学
细胞分化
组蛋白H3
生物
生物化学
基因
甲基化
作者
Qian Zhang,Liqun Xu,Yixuan Wang,Qian Zhang,Tong Xue,Quan Sun,Hao Tang,Ari Melnick,Xinsheng Cao,Fei Shi,Ge Zhang,Shu Zhang,Zebing Hu
标识
DOI:10.1016/j.cellsig.2022.110554
摘要
Emerging evidence indicates that multiple mechanisms are involved in bone loss induced by mechanical unloading. Thus far, few study has established the pathophysiological role of histone modification for osteogenic differentiation under mechanical unloading. Here we demonstrated that the histone H3 lysine 9 (H3K9) methyltransferase Setdb1, which was sensitive to mechanical unloading, was increased during osteogenic differentiation of MC3T3-E1 cells for the first time. Knockdown of Setdb1 significantly blocked osteoblast function in vivo and in vitro. Through bioinformatics analysis of candidate miRNAs regulated by H3K9me3, we further identified that Setdb1 inhibited the expression of miR-212-3p by regulating the formation of H3K9me3 in the promoter region. Mechanically, we revealed that miR-212-3p was upregulated under mechanical unloading and suppressed osteogenic differentiation by directly downregulating High mobility group box 1 protein (Hmgb1) expression. Furthermore, we verified the molecular mechanism of the SETDB1/miR-212-3p/HMGB1 pathway in hFOB cells under mechanical unloading. In summary, these data demonstrate the essential function of the Setdb1/miR-212-3p/Hmgb1 pathway in osteogenic differentiation under mechanical unloading, and present a potential protective strategies against bone loss induced by mechanical unloading.
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