N6-Methyladenosine in Cell-Fate Determination of BMSCs: From Mechanism to Applications.

The methylation of adenosine base at the nitrogen-6 position is referred to as "N6-methyladenosine (mA)" and is one of the most prevalent epigenetic modifications in eukaryotic mRNA and noncoding RNA (ncRNA). Various mA complex components known as "writers," "erasers," and "readers" are involved in the function of mA. Numerous studies have demonstrated that mA plays a crucial role in facilitating communication between different cell types, hence influencing the progression of diverse physiological and pathological phenomena. In recent years, a multitude of functions and molecular pathways linked to mA have been identified in the osteogenic, adipogenic, and chondrogenic differentiation of bone mesenchymal stem cells (BMSCs). Nevertheless, a comprehensive summary of these findings has yet to be provided. In this review, we primarily examined the mA alteration of transcripts associated with transcription factors (TFs), as well as other crucial genes and pathways that are involved in the differentiation of BMSCs. Meanwhile, the mutual interactive network between mA modification, miRNAs, and lncRNAs was intensively elucidated. In the last section, given the beneficial effect of mA modification in osteogenesis and chondrogenesis of BMSCs, we expounded upon the potential utility of mA-related therapeutic interventions in the identification and management of human musculoskeletal disorders manifesting bone and cartilage destruction, such as osteoporosis, osteomyelitis, osteoarthritis, and bone defect.