Methyltransferase-Like 3-Mediated N6-Methyladenosine Modification on RNAs: A Novel Perspective for the Pathogenesis and Treatment of Bone Diseases

Abstract

Osteoarthritis, osteoporosis, and osteosarcoma are prevalent osseous pathologies associated with the aberrant functionality of chondrocytes, osteoclasts, and osteoblasts, respectively. These conditions frequently exhibit therapeutic resistance and possess a high mortality risk, thus representing substantial health threats. To mitigate these concerns, it is imperative to investigate novel mechanistic insights. Methyltransferase-like 3 (METTL3) is pivotal in these disorders by modulating gene expression via N⁶-methyladenosine (m⁶A) modifications on RNA, thereby impacting cellular processes. Although considerable research has elucidated METTL3's involvement in these diseases, a systematic review is essential to summarise these findings and evaluate METTL3's significance. This review endeavours to aggregate and examine contemporary studies to elucidate METTL3's role in bone pathologies and its clinical implications. We propose that METTL3 constitutes a risk gene in these conditions by mediating m⁶A modifications on both mRNAs and non-coding RNAs, suggesting that METTL3 may serve as a critical diagnostic biomarker and therapeutic target. In conclusion, this review provides an extensive analysis of METTL3 and its correlation with osteoarthritis, osteoporosis, and osteosarcoma, offering valuable perspectives on extant research and serving as a valuable reference for researchers engaged in both basic and translational studies.