The emerging roles of N6-methyladenosine in osteoarthritis

Abstract

Finding new biomarkers and molecular targets to guide OA treatment remains a significant challenge. One of the most frequent forms of RNA methylation, N⁶-methyladenosine (m⁶A), can affect gene expression and RNA transcription, processing, translation, and metabolism. Osteoarthritis (OA) can cause disability and pain degenerative disease, reduce the quality of life of the elderly, and increase the social and economic burden. Changes in m⁶A levels are crucial in OA progress. In this review, the discussion will concentrate on the role that m⁶A plays in OA occurrence and progression. The m⁶A involved in the OA process mainly includes METTL3 and FTO. Current studies on m⁶A and OA primarily focus on four signaling pathways, namely, NF-κB, LNCRNAs, ATG7, and Bcl2. m⁶A participates in these signaling pathways and affects cellular inflammation, apoptosis, senescence, and autophagy, thus controlling the OA process. The modification of m⁶A affects so many signaling pathways. For the treatment of OA, it may represent a viable new therapeutic target.

Keywords: LncRNAs; N6-methyladenosine; apoptosis; autophagy; inflammation; osteoarthritis; senescence.

Figure 1

The role of m⁶A regulators in ATDC5, FLSs, SWB53, and Chondrocytes. ADAMTS-5, a disintegrin and metalloproteinase with thrombospondin motifs-5; ATG7, autophagy related protein 7; COL2A1, collagen type II alpha 1; Coll II, type II collagen; ECM, extracellular matrix; FLSs, fibroblast like synoviocytes; FTO, fat mass and obesity-associated protein; IL, interleukin; LC3B-II, microtubule-associated protein 1 light chain 3B-II; MMP, matrix metalloproteinase NF-κB, nuclear factor-κB; p-p65, phosphorylated-p65; TIMP, tissue inhibitors of metalloprotease; TNF-α, tumor necrosis factor alpha; YTHDF, YTH N⁶-methyladenosine RNA binding protein.