The essential roles of m⁶A modification in osteogenesis and common bone diseases

N6-methyladenosine (m⁶A) is the most prevalent modification in the eukaryotic transcriptome and has a wide range of functions in coding and noncoding RNAs. It affects the fate of the modified RNA, including its stability, splicing, and translation, and plays an important role in post-transcriptional regulation. Bones play a key role in supporting and protecting muscles and other organs, facilitating the movement of the organism, ensuring blood production, etc. Bone diseases such as osteoarthritis, osteoporosis, and bone tumors are serious public health problems. The processes of bone development and osteogenic differentiation require the precise regulation of gene expression through epigenetic mechanisms including histone, DNA, and RNA modifications. As a reversible dynamic epigenetic mark, m⁶A modifications affect nearly every important biological process, cellular component, and molecular function, including skeletal development and homeostasis. In recent years, studies have shown that m⁶A modification is involved in osteogenesis and bone-related diseases. In this review, we summarized the proteins involved in RNA m⁶A modification and the latest progress in elucidating the regulatory role of m⁶A modification in bone formation and stem cell directional differentiation. We also discussed the pathological roles and potential molecular mechanisms of m⁶A modification in bone-related diseases like osteoporosis and osteosarcoma and suggested potential areas for new strategies that could be used to prevent or treat bone defects and bone diseases.