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Interaction Between YTH Domain-Containing Family Protein 2 and SET Domain-Containing Lysine Methyltransferase 7

Lexiang Li1, Jun Zhu1, Yi Chen1

  • 1Department of Joint Surgery and Orthopedic Medicine, Shanghai Changzheng Hospital (The Second Affiliated Hospital of Naval Medical University), Shanghai, China.

The Journal of Gene Medicine
|January 10, 2025
PubMed
Abstract

Insights

SET domain-containing lysine methyltransferase 7 (SETD7) promotes osteoarthritis (OA) by impairing chondrocyte autophagy and increasing inflammation. Targeting the YTHDF2/SETD7 interaction may offer new therapeutic strategies for OA.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Background:

  • Osteoarthritis (OA) involves cartilage degeneration driven by inflammatory and autophagic pathways.
  • SET domain-containing lysine methyltransferase 7 (SETD7) is implicated in OA pathogenesis.

Purpose of the Study:

  • Investigate SETD7 expression in OA.
  • Determine SETD7's role in interleukin-1 beta (IL-1β)-induced chondrocyte injury.
  • Elucidate SETD7's modulation of autophagy and inflammation.

Main Methods:

  • Quantified SETD7 expression in OA cartilage via RT-qPCR and Western blot.
  • Used si-SETD7 in IL-1β-treated human articular chondrocytes (HACs) to assess viability, apoptosis, inflammation, and autophagy.
  • Explored YTHDF2 and SETD7 interaction using RNA immunoprecipitation and co-immunoprecipitation.

Main Results:

  • SETD7 was overexpressed in OA cartilage and increased with IL-1β treatment.
  • SETD7 knockdown improved chondrocyte viability, reduced apoptosis, and modulated inflammatory markers and antioxidant enzymes.
  • SETD7 knockdown restored autophagy, an effect negated by chloroquine; YTHDF2 stabilized SETD7 mRNA.

Conclusions:

  • SETD7 critically contributes to OA pathogenesis by affecting chondrocyte survival, apoptosis, inflammation, and autophagy.
  • The YTHDF2/SETD7 interaction exacerbates chondrocyte injury in OA.
  • The YTHDF2/SETD7 axis presents a novel therapeutic target for OA treatment.
Keywords:
SET domain‐containing lysine methyltransferase 7YTH domain‐containing family protein 2chloroquineosteoarthritis

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