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Abstract N6-methyladenosine (m6A) modification, catalyzed by methyltransferase complexes (MTCs), plays many roles in multifaceted biological activities. As the most important subunit of MTCs, the METTL3-METTL14 complex is reported to be the initial factor that catalyzes the methylation of adenosines. Recently, accumulating evidence has indicated that the METTL3-METTL14 complex plays a key role in musculoskeletal diseases in an m6A-dependent or -independent manner. Although the functions of m6A modifications in a variety of musculoskeletal diseases have been widely recognized, the critical role of the METTL3-METTL14 complex in certain musculoskeletal disorders, such as osteoporosis, osteoarthritis, rheumatoid arthritis and osteosarcoma, has not been systematically revealed. In the current review, the structure, mechanisms and functions of the METTL3-METTL14 complex and the mechanisms and functions of its downstream pathways in the aforementioned musculoskeletal diseases are categorized and summarized.

Abstract Osteoporosis, which is caused by an imbalance in osteoblasts and osteoclasts, is a global age-related metabolic disease. Osteoblasts induce osteocyte and bone matrix formation, while osteoclasts play an important role in bone resorption. Maintaining a balance between osteoblast formation and osteoclastic absorption is crucial for bone remodeling. Circular RNAs (circRNAs), which are characterized by closed-loop structures, are a class of novel endogenous transcripts with limited protein-coding abilities. Accumulating evidence indicates that circRNAs play important roles in various bone diseases, such as osteosarcoma, osteoarthritis, osteonecrosis, and osteoporosis. Recent studies have shown that circRNAs regulate osteoblast and osteoclast differentiation and may be potential biomarkers for osteoporosis. In the current review, we summarize the expression, function, and working mechanisms of circRNAs involved in osteoblasts, osteoclast differentiation, and osteoporosis.