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The Effect of JAK Inhibitor Tofacitinib on Chondrocyte Autophagy

Ping Zhang1, Juan Xiao1, Chenggen Luo1

  • 1Department of Rheumatology and Immunology, Affiliated Hospital of Zunyi Medical University, Huichuan District, 149 Dalian Road, Zunyi, 563003, China.

Inflammation
|June 13, 2023
PubMed

Insights

Tofacitinib, a JAK inhibitor, shows promise in treating osteoarthritis (OA) by reducing inflammation and restoring cartilage health. It protects cartilage extracellular matrix and enhances chondrocyte autophagy in OA models.

Area of Science:

  • Biochemistry
  • Cell Biology
  • Pharmacology

Background:

  • Osteoarthritis (OA) is a degenerative joint disease with no current cure.
  • The pathogenesis of OA involves complex inflammatory and matrix degradation processes.
  • Janus kinase (JAK) inhibitors, like tofacitinib, possess anti-inflammatory properties.

Purpose of the Study:

  • To investigate tofacitinib's effect on cartilage extracellular matrix in OA.
  • To determine if tofacitinib protects chondrocytes by inhibiting JAK1/STAT3 signaling and upregulating autophagy.
  • To evaluate tofacitinib's therapeutic potential in experimental OA models.

Main Methods:

  • In vitro OA model using SW1353 cells stimulated with interleukin-1β (IL-1β).
  • In vivo OA model induced by the modified Hulth method in rats.
  • Analysis of matrix metalloproteinases (MMPs), collagen II, autophagy markers (beclin1, LC3-II/I, p62), and JAK1/STAT3 pathway activation.

Main Results:

  • IL-1β induced OA-like changes in vitro, increasing MMPs and decreasing collagen II and autophagy markers.
  • Tofacitinib treatment attenuated IL-1β-induced matrix degradation and restored autophagy in vitro.
  • Tofacitinib inhibited the JAK1/STAT3 pathway activation and nuclear translocation of p-STAT3.
  • In vivo, tofacitinib reduced cartilage degeneration and enhanced chondrocyte autophagy in a rat OA model.

Conclusions:

  • Chondrocyte autophagy is impaired in experimental OA models.
  • Tofacitinib demonstrates a protective effect against cartilage degeneration in OA.
  • Tofacitinib reduces inflammation and restores autophagic flux in OA by inhibiting the JAK1/STAT3 pathway.
Keywords:
AutophagyChondrocytesJAK1/STAT3OsteoarthritisTofacitinib

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