ALKBH5 facilitates CYP1B1 mRNA degradation via m6A demethylation to alleviate MSC senescence and osteoarthritis progression

• DOI: 10.1038/s12276-023-01059-0
• Publication Date: 2023-08-01T01:02:09Z
• Authors: Guiwen Ye; Jinteng Li; Wenhui Yu; Zhongyu Xie; Guan Zheng; Wenjie Liu; Shan Wang; Qian Cao; Jiajie Lin; Zepeng Su; Dateng Li; Yunshu Che; Shuai Fan; Peng Wang; Yanfeng Wu; Huiyong Shen
• Keywords: Senescence; Knockout mouse

Improving health and delaying aging is the focus of medical research. Previous studies have shown that mesenchymal stem cell (MSC) senescence closely related to organic development aging-related diseases such as osteoarthritis (OA). m6A a common RNA modification plays an important role in regulating biological functions, ALKBH5 one key demethylases. However, MSC still unclear. Here, we found level was enhanced expression decreased MSCs induced by multiple replications, H2O2 stimulation or UV irradiation. Downregulation facilitated enhancing stability CYP1B1 mRNA inducing mitochondrial dysfunction. In addition, IGF2BP1 identified reader restraining degradation m6A-modified mRNA. Furthermore, Alkbh5 knockout aggravated spontaneous OA mice, overexpression improved efficacy OA. Overall, this study revealed novel mechanism promising targets protect against