m⁶A modification in skeletal system diseases (Review)

N6‑methyladenosine (m⁶A) modifications are key epigenetic regulatory mechanisms in mammals and serve key roles in both normal skeletal development and the pathogenesis of skeletal disorder. The dynamic and reversible regulation of m⁶A relies on three core factors: Methyltransferases (writers), demethylases (erasers) and m⁶A‑binding proteins (readers), which collectively ensure proper physiological functions. Despite this, the functions and regulatory mechanisms of numerous m⁶A‑associated factors in skeletal diseases remain insufficiently understood. m6A modification maintains bone homeostasis during skeletal development primarily by regulating the balance between osteoblasts and osteoclasts. Under pathological conditions, dysregulated m⁶A modification contributes to aberrant osteoclast proliferation and chondrocyte apoptosis, leading to bone loss and cartilage degeneration. These pathological changes are key contributors to common types of skeletal disorder, including osteoporosis, osteoarthritis, rheumatoid arthritis and intervertebral disc degeneration, imposing a burden on human health. Non‑coding RNAs are major targets of m⁶A modification and their interactions exert post‑transcriptional regulation in skeletal biology. The present review summarizes the roles and mechanisms of m⁶A modification in skeletal diseases and highlights its therapeutic potential, offering novel perspectives for disease prevention and treatment.