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.

Keywords: N6-methyladenosine; biomarker; molecular mechanisms; osteoarthritis; therapeutic target.

FIGURE 1

RNA methylation modification process. Writers, erasers and readers add, remove and identify methyl groups respectively. This process makes the m6A modification flexible and reversible.

FIGURE 2

m6A modification in bone development. M6a modification regulates osteoblast differentiation by regulating MBP2 gene expression and the PTH/Pth1r signaling axis. In addition, m6a modification also promotes the process of bone resorption by regulating the expression of RANK gene.

FIGURE 3

Molecular mechanisms of m6a modifications in the pathogenesis of OA. M6A modification ultimately cause cartilage apoptosis, cellular senescence, increased inflammatory response and extracellular matrix imbalance through regulation of gene expression and signaling pathways.