Regulatory Role of N6-Methyladenosine (m6A) Modification in Osteoarthritis

Abstract

Osteoarthritis (OA) is the most common joint disease, usually occurring in middle-aged and elderly people. However, current treatment for OA in its early stages is ineffective, and drug therapy is often ineffective in slowing the progression of the disease. In fact, a deeper understanding of the underlying molecular mechanisms of OA could help us to better develop effective therapeutic measures. N6-methyladenosine (m6A) is a methylation that occurs at the adenosine N6-position, which is the most common internal modification on eukaryotic mRNAs. The role and mechanisms of m6A in mammalian gene regulation have been extensively studied. The “Writer”, “eraser”, and “reader” proteins are key proteins involved in the dynamic regulation of m6A modifications. Recent studies on post-transcriptional regulation alone have shown that m6a modification has an important role in the development of OA. This paper summarizes the specific regulatory processes of M6A in disease and reviews the role of m6A in OA, describing its pathophysiological role and molecular mechanisms, as well as its future research trends and potential clinical applications in OA.

N6-methyladenosine (m6A) reader IGF2BP1 facilitates clear-cell renal cell carcinoma aerobic glycolysis

“…Methyltransferase installed the m 6 A modification on mRNA, including methyltransferase-like 3 (METTL3), methyltransferase-like 14 (METTL14), and the Wilms tumor 1-associated protein (WTAP) ( Lin et al, 2022 ; Luo et al, 2022 ). In addition, the m 6 A modification was wiped by demethylase, including obesity-associated protein (FTO) and alkB homolog 5 (ALKBH5) ( Qin et al, 2022 ; Zhai et al, 2022 ). In ccRCC, the function of m 6 A has been gradually verified.…”

FTO-mediated m6A demethylation of pri-miR-3591 alleviates osteoarthritis progression

“…[ 8 , 9 ]. Previous studies have attested that dysregulation of m 6 A modification and its related genes participate in the development of OA [ 10 – 13 ]. The earliest discovered FTO catalyzes m6A demethylation in a Fe(II)—and α-ketoglutarate-dependent manner [ 14 ].…”

Autophagy-related genes and pathways was associated with osteoarthritis pathogenesis

“…Inhibition PI3K/AKT/mTOR signaling pathway involved in cellular autophagy by NOV/CCN3 ameliorated the IL-1βinduced matrix catabolism and in ammatory and promoted the expression of Atg5 and Beclin1 for cartilage protection 17,18,19 . In addition, epigenetics modi cation (microRNA, lncRNA) regulated autophagy pathway to affect the develop of osteoarthritis 20,21,22,23 . MiR-155, miR-27a 24 , miR-34a, miR-449a, miR-9, miR-140-5p, miR-20, miR-146a and miR-149 regulated osteoarthritis generation and development by targeting autophagy-related genes (SIRT1, ULK1, FUT1, ATG10, BCL2 and so on).…”