Work

The progress of m6A methylation-regulated non-coding RNAs in osteogenic differentiation and osteoporosis

Year: 2025

Type: article

Abstract: N6-methyladenosine (m6A) is the most abundant internal modification of eukaryotic RNA, and has increasingly been recognized as a critical regulator of gene expression at both the transcriptional and post-transcriptional levels. The m6A modification process is highly dynamic and reversible, governed by methyltransferase writers (e.g., METTL3, METTL14, WTAP), demethylase erasers (such as FTO and ALKBH5), and specific readers (including YTHDF and IGF2BP protein families) that interpret the modification and mediate its downstream effects. Accumulating evidence indicates that m6A-mediated regulation of non-coding RNAs (ncRNAs) plays a pivotal role in osteogenic differentiation, a process central to bone formation. Impaired osteogenesis, which contributes to decreased bone mass, is closely linked to the onset and progression of osteoporosis. This review summarizes recent progress on the interplay between m6A modification and ncRNAs in osteogenic differentiation, and outlines a regulatory framework, the m6A-ncRNA-target gene axis, that includes m6A modification, ncRNA interactions, and downstream signaling pathways, such as Wnt/β-catenin and BMP/Smad, and discusses their potential as biomarkers or therapeutic targets for osteoporosis, with the goal of providing new insights into the epigenetic mechanisms underlying osteoporosis and to identify potential molecular targets for future therapeutic strategies.

Source: Non-coding RNA Research

DOI: 10.1016/j.ncrna.2025.11.005