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Review
. 2025 May 21;26(10):4955.
doi: 10.3390/ijms26104955.

RNA Modifications in Osteoarthritis: Epitranscriptomic Insights into Pathogenesis and Therapeutic Targets

Shabnam Radbakhsh  1 , Mehdi Najar  1 , Makram Merimi  1 , Mohamed Benderdour  1 , Julio C Fernandes  1 , Johanne Martel-Pelletier  1 , Jean-Pierre Pelletier  1 , Hassan Fahmi  1
Affiliations
Review

RNA Modifications in Osteoarthritis: Epitranscriptomic Insights into Pathogenesis and Therapeutic Targets

Shabnam Radbakhsh et al. Int J Mol Sci. .

Abstract

Osteoarthritis (OA) is a chronic joint disorder characterized by progressive degeneration of articular cartilage, pain, synovial inflammation, and bone remodeling. Post-transcriptional RNA modifications, known as epitranscriptome, are a group of biochemical alterations in the primary RNA transcript that might influence RNA structure, stability, and function. Different kinds of RNA modifications have been recognized, such as methylation, acetylation, pseudouridylation, and phosphorylation. N6-methyladenosine (m6A), 5-methylcytosine (m5C), N7-methylguanosine (m7G), 2'-O-ribose methylation (2'-O-Me), and pseudouridylation (Ψ) are the most prevalent RNA modifications. Recent studies have shown that disruption in these modifications can interfere with gene expression and protein function. Here, we will review all types of RNA modifications and how they contribute to the onset and progression of OA. To the best of our knowledge, this is the first review comprehensively addressing all epitranscriptomic modifications in OA.

Keywords: 2′-O-ribose methylation; 5-methylcytosine; N6-methyladenosine; N7-methylguanosine; RNA modification; epitranscriptomics; inflammation; osteoarthritis.

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Conflict of interest statement

The authors declare no conflicts of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results.

Figures

Figure 1
Figure 1
Representative chemical structures of common RNA methylation modifications: (a) N6-methyladenosine (m6A), (b) N1-methyladenosine (m1A), (c) 5-methylcytidine (m5C), and (d) 7-methylguanosine (m7G), highlighting the positions where methyl groups are added to the respective nucleosides.
Figure 2
Figure 2
Schematic representation of RNA modifications and their regulatory proteins. The diagram illustrates the dynamic regulation of RNA modifications by writer, eraser, and reader proteins. Writer proteins (e.g., METTL3, METTL14, NSUN2, NRMT, CMTR1, and PUS) catalyze the addition of modifications such as m6A, m5C, ψ, and m7G. Eraser proteins (e.g., FTO, ALKBH5, and TET) remove specific modifications, and reader proteins (e.g., YTHDF1/2/3, IGF2BP1/2/3, THOC1/2, ALYREF, and EIF4E) recognize these modifications and regulate RNA function and cellular responses.
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