2. Academic Validation
  3. ALKBH5 mediates FGF21 m6A demethylation in human bone marrow mesenchymal stem cells under high glucose conditions

ALKBH5 mediates FGF21 m6A demethylation in human bone marrow mesenchymal stem cells under high glucose conditions

  • Biochem Biophys Res Commun. 2025 Aug 8:774:152042. doi: 10.1016/j.bbrc.2025.152042.
Zhenpeng Wang 1,  Yan Tang 2,  Yin Liu 3,  Yuping Zeng 4,  Mei Zhang 5
Affiliations

Affiliations

  • 1 Department of Laboratory Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan province, China. Electronic address: 2992006367@qq.com.
  • 2 Department of Clinical Laboratory, Deyang People's Hospital, Deyang, Sichuan province, China. Electronic address: 15184387003@163.com.
  • 3 Department of Laboratory Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan province, China. Electronic address: liuyin14@163.com.
  • 4 Department of Laboratory Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan province, China. Electronic address: zypjyk@163.com.
  • 5 Department of Laboratory Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan province, China. Electronic address: meizhang@wchscu.cn.
PMID: 40441069 DOI: 10.1016/j.bbrc.2025.152042
Abstract

Diabetic osteoporosis (DOP), a chronic complication of diabetes mellitus (DM), often remains undetected until a fracture occurs due to its insidious nature. Although RNA methylation modification is known to play a critical role in various diseases and bone formation processes, its role in the pathogenesis of DOP has not been explored enough. Here we revealed the regulatory role of ALKBH5 in the demethylation of FGF21 N6-methyladenosine (m6A) and its underlying mechanisms in DOP. In the experiments, we observed the reduced-total RNA m6A level and elevated-ALKBH5 expression in human bone marrow mesenchymal stem cells (hBMSCs) under high glucose (HG) conditions, while knockdown of ALKBH5 enhanced the m6A methylation of FGF21 mRNA and promoted the interaction between FGF21 mRNA and YTHDF2 reading protein, up-regulating bone formation-related genes. Our study reveals the possible role of ALKBH5 in regulating osteogenic differentiation and provides a new insight into the treatment of clinical DOP.

Keywords

ALKBH5; Diabetic osteoporosis; FGF21; m6A demethylation.

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