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Updated: May 28, 2025

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WISP1 promotes the progression of rheumatoid arthritis through NLRP3 inflammasome activation

Tiantian Hao1, Jianhua Niu2, Zizheng Tang3

  • 1Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, Shandong 250117, People's Republic of China.

Molecular Immunology
|February 12, 2025
PubMed
Abstract

Insights

Targeting WNT1 inducible signaling pathway protein 1 (WISP1) by knockdown effectively reduced inflammation and joint damage in rheumatoid arthritis (RA) models. This approach inhibited NLRP3 inflammasome activation, offering a potential therapeutic strategy for RA.

Area of Science:

  • Immunology
  • Molecular Biology
  • Rheumatology

Background:

  • Rheumatoid arthritis (RA) is a chronic autoimmune disease with limited effective treatments.
  • WNT1 inducible signaling pathway protein 1 (WISP1) is investigated as a novel therapeutic target for RA.
  • Understanding WISP1's role in RA pathogenesis is crucial for developing new interventions.

Purpose of the Study:

  • To investigate the therapeutic potential of WISP1 knockdown in a rat model of collagen-induced arthritis (CIA).
  • To examine the effects of WISP1 knockdown on pro-inflammatory factors and NLRP3 inflammasome activation in RA.
  • To evaluate the impact of WISP1 knockdown on the biological behavior of fibroblast-like synoviocytes (FLSs) in vitro.

Main Methods:

  • Adeno-associated virus-mediated short hairpin RNA (AAV-shRNA) was used to knockdown WISP1 in CIA rats.
  • Tumor necrosis factor-alpha (TNF-α)-induced FLSs were transfected with small interfering RNA (siRNA) targeting WISP1.
  • Inflammatory markers, cell viability, migration, invasion, and NLRP3 inflammasome activation were assessed using qRT-PCR, ELISA, western blot, CCK-8, wound-healing, and transwell assays.

Main Results:

  • WISP1 knockdown significantly improved joint damage and reduced synovial inflammation in CIA rats.
  • Knockdown of WISP1 suppressed TNF-α-induced proliferation, migration, and invasion of FLSs.
  • WISP1 knockdown attenuated the secretion of pro-inflammatory factors and inhibited NLRP3 inflammasome activation in both CIA rats and TNF-α-induced FLSs.

Conclusions:

  • WISP1 knockdown demonstrates significant therapeutic potential for rheumatoid arthritis.
  • Inhibition of WISP1 effectively suppresses NLRP3 inflammasome activation and inflammatory mediator production.
  • Targeting WISP1 presents a promising strategy for managing RA by mitigating inflammation and joint destruction.
Keywords:
NLRP3 inflammasomeRheumatoid arthritisWISP1

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