Multifaceted Functions and Novel Insight Into the Regulatory Role of RNA N6-Methyladenosine Modification in Musculoskeletal Disorders

Abstract

RNA modifications have emerged as key regulators of transcript expression in diverse physiological and pathological processes. As one of the most prevalent types of RNA modifications, N 6 -methyladenosine (m 6 A) has become the highlight in modulation of various diseases through interfering RNA splicing, translation, nuclear export, and decay. In many cases, the detailed functions of m 6 A in cellular processes and diseases remain unclear. Notably, recent studies have determined the relationship between m 6 A modification and musculoskeletal disorders containing osteosarcoma, osteoarthritis, rheumatoid arthritis, osteoporosis, etc. Herein, this review comprehensively summarizes the recent advances of m 6 A modification in pathogenesis and progression of musculoskeletal diseases. Specifically, the underlying molecular mechanisms, detection technologies, regulatory functions, clinical implications, and future perspectives of m 6 A in musculoskeletal disorders are discussed, with the aim to provide a novel insight into their association.

Circular RNAs in osteoarthritis: indispensable regulators and novel strategies in clinical implications

“…Nevertheless, studies have uncovered novel interactions between circRNAs and multiple biological and pathological processes. For example, N6-methyladenosine (m 6 A) modification [139], the most abundant post-transcriptional RNA modification in mammals [140], has been demonstrated to regulate circRNA translation, degradation, export, etc. [141].…”

Role of m6A in osteoporosis, arthritis and osteosarcoma (Review)

“…In addition, several bone-related diseases are associated with the activities of m6A, such as epigenetic m6A modification, which plays an important role in the ossification of the ligamentum flavum ( 199 ). Recently, a review summarized the association between m6A and musculoskeletal disorders ( 200 ). However, the roles of m6A in T cell homoeostasis and differentiation remain unclear, both of which closely associated with the occurrence and development of osteoporosis, osteoarthritis, rheumatoid arthritis and osteosarcoma, which is a subject of novel and extensive research.…”

m6A RNA Methylation in Systemic Autoimmune Diseases—A New Target for Epigenetic-Based Therapy?

“…The relationship between RNA-associated epigenetic changes have been recently proposed to be another layer of epigenetic regulation that might unravel the mystery of RA pathogenesis [ 155 ]. As it is a new pathway of epigenetic studies, still in its infancy, the available data are relatively rare.…”