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Updated: Jan 11, 2026

Software-Assisted Quantitative Measurement of Osteoarthritic Subchondral Bone Thickness
Published on: March 18, 2022
NSUN3-mediated m5C modification of FABP5 regulates lipid droplets through autophagy to alleviate osteoarthritis
Ziwei Luo1, Yuanxian Liu2, Baorong Cheng1
1Shenzhen Hospital of Integrated Traditional Chinese and Western Medicine, Shenzhen 518104, PR China; Shenzhen Clinical College of Integrated Chinese and Western Medicine, Guangzhou University of Chinese Medicine, Shenzhen 518104, PR China.
Abstract:
Lipid droplets (LDs) are closely associated with the onset and progression of osteoarthritis (OA). RNA 5-Methylcytosine (m5C) modification plays a key role in various diseases, but its role in the pathogenesis of OA is largely unknown. In this study, NSUN3 expression was the most significantly down-regulated methyltransferase of the NSUN family in OA. Overexpression of NSUN3 alleviated OA by promoting autophagy to clear abnormal lipid accumulation in chondrocytes, whereas siNSUN3 had the opposite effect. Mechanistically, NSUN3 mediated m5C modification of FABP5 mRNA and enhanced its mRNA stability. Intra-articular injection of AAV-NSUN3 attenuated OA in rats. Overall, NSUN3 might be a potential therapeutic target for OA and even for dysregulated LDs in a wide range of diseases.
Insights
Osteoarthritis (OA) involves lipid droplets (LDs). Researchers found that NSUN3, a methyltransferase, alleviates OA by enhancing autophagy and stabilizing FABP5 mRNA, suggesting NSUN3 as a potential therapeutic target for OA and LD-related diseases.
Area of Science:
- Biochemistry
- Molecular Biology
- Pathology
Background:
- Lipid droplets (LDs) are implicated in osteoarthritis (OA) pathogenesis.
- The role of RNA 5-Methylcytosine (m5C) modification in OA is not well understood.
Purpose of the Study:
- To investigate the role of NSUN3, a methyltransferase, in OA.
- To explore the mechanism by which NSUN3 affects OA progression.
Main Methods:
- Analysis of NSUN family methyltransferase expression in OA.
- Overexpression and knockdown of NSUN3 in chondrocytes.
- Assessment of autophagy and lipid accumulation.
- Investigation of NSUN3's effect on FABP5 mRNA stability.
- In vivo study using a rat model of OA with AAV-NSUN3 injection.
Main Results:
- NSUN3 was significantly downregulated in OA.
- NSUN3 overexpression reduced OA symptoms by promoting autophagy and clearing lipid accumulation in chondrocytes.
- NSUN3 mediated m5C modification of FABP5 mRNA, increasing its stability.
- AAV-NSUN3 injection attenuated OA in a rat model.
Conclusions:
- NSUN3 plays a protective role in OA by regulating lipid metabolism and autophagy.
- NSUN3's mechanism involves m5C modification of FABP5 mRNA.
- NSUN3 represents a potential therapeutic target for OA and other diseases characterized by dysregulated lipid droplets.