Novel insights into the interaction between N6‐methyladenosine methylation and noncoding RNAs in musculoskeletal disorders

Background Musculoskeletal disorder (MSD) are a class of inflammatory and degener‐ative diseases, but the precise molecular mechanisms are still poorly understood. Noncoding RNA (ncRNA) N6‐methyladenosine (m6A) modification plays an essential role in the pathophysiological process of MSD. This review summarized the interaction between m6A RNA methylation and ncRNAs in the molecular regulatory mechanism of MSD. It provides a new perspective for the pathophysiological mechanism and ncRNA m6A targeted therapy of MSD. Methods A comprehensive search of databases was conducted with musculoskeletal disorders, noncoding RNA, N6‐methyladenosine, intervertebral disc degeneration, osteoporosis, osteosarcoma, osteoarthritis, skeletal muscle, bone, and cartilage as the key‐words. Then, summarized all the relevant articles. Results Intervertebral disc degeneration (IDD), osteoporosis (OP), osteosarcoma (OS), and osteoarthritis (OA) are common MSDs that affect muscle, bone, cartilage, and joint, leading to limited movement, pain, and disability. However, the precise pathogenesis remains unclear, and no effective treatment and drug is available at present. Numerous studies confirmed that the mutual regulation between m6A and ncRNAs (i.e., microRNAs, long ncRNAs, and circular RNAs) was found in MSD, m6A modification can regulate ncRNAs, and ncRNAs can also target m6A regulators. ncRNA m6A modification plays an essential role in the pathophysiological process of MSDs by regulating the homeostasis of skeletal muscle, bone, and cartilage. Conclusion m6A interacts with ncRNAs to regulate multiple biological processes and plays important roles in IDD, OP, OS, and OA. These studies provide new insights into the pathophysiological mechanism of MSD and targeting m6A‐modified ncRNAs may be a promising therapy approach. m6A regulates the expression and function of ncRNAs (i.e., miRNAs, lncRNAs and circRNAs), ncRNAs can also affect m6A‐related protein. m6A‐related proteins in ncRNA are abnormally expressed and closely associated with bone osteogenic, osteoclastogenic processes and myogenesis, participating in modulating the homoeostasis of skeletal muscle, bone and cartilage. ncRNA m6A modification regulates the pathological and physiological processes of musculoskeletal disorders (i.e., IDD, OP, OS and OA). In IDD, ncRNA m6A modification regulated NP cells glucose metabolism, senescence and pyroptosis. In OP, ncRNA m6A modification regulated BMSCs osteogenic differentiation, osteobl