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.

Cellular Signalling
|November 12, 2025
PubMed

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.