AlkB homolog 5 (ALKBH5) has been reported as a key m6A demethylase that is involved in development and diseases; however, the function of ALKBH5 in osteogenesis remains unknown. In this study, we report that ALKBH5 mRNA and protein expression were upregulated during osteoblast differentiation and that ALKBH5 knockdown suppressed osteoblast differentiation, mineralization, and the expression of osteogenic biomarkers. Conversely, ALKBH5 overexpression promoted osteogenesis. Moreover, the expression of wild-type ALKBH5, but not the m6A-modified active site mutant ALKBH5, could rescue ALKBH5 knockdown-induced osteogenesis inhibition. Furthermore, knockdown of ALKBH5 significantly impaired the mRNA stability of the transcription factor Runx2, which plays a key role in osteoblast differentiation. Taken together, our results suggest that ALKBH5 promotes osteogenesis through modulating Runx2 mRNA stability.

中文翻译：

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RNA 去甲基化酶 ALKBH5 通过调节 Runx2 mRNA 稳定性促进成骨细胞分化

据报道，AlkB 同源物 5 (ALKBH5) 是参与发育和疾病的关键 m6A 脱甲基酶；然而，ALKBH5 在成骨中的功能仍然未知。在这项研究中，我们报告了 ALKBH5 mRNA 和蛋白质表达在成骨细胞分化过程中上调，并且 ALKBH5 敲低抑制了成骨细胞分化、矿化和成骨生物标志物的表达。相反，ALKBH5 过表达促进成骨。此外，野生型 ALKBH5 的表达，而不是 m6A 修饰的活性位点突变体 ALKBH5，可以挽救 ALKBH5 敲低诱导的成骨抑制。此外，ALKBH5 的敲低显着损害了转录因子 Runx2 的 mRNA 稳定性，Runx2 在成骨细胞分化中起关键作用。综合起来，