WISP1 promotes the progression of rheumatoid arthritis through NLRP3 inflammasome activation

Mol Immunol. 2025 Mar;179:106-115. doi: 10.1016/j.molimm.2025.02.004. Epub 2025 Feb 11.

ABSTRACT

BACKGROUND: Rheumatoid arthritis (RA) is a chronic autoimmune disease without effective treatments. This study explored WNT1 inducible signaling pathway protein 1 (WISP1) as a potential target to prevent RA.

METHODS: AAV-shRNA-WISP1 or AAV-NC was injected in each ankle of collagen-induced arthritis (CIA) rats. Si-WISP1 or NC vector was transfected to TNF-α-induced fibroblast-like synoviocytes (FLSs). The effects of WISP1 knockdown on levels of pro-inflammatory factors in rats or FLSs were examined by qRT-PCR, ELISA, and western blot. CCK-8, Wound-healing, and transwell assays were used to estimate the effects of WISP1 knockdown on TNF-α-induced cell vitality, migration, and invasion in FLSs. The NLRP3 inflammasome-related proteins were checked by immunohistochemistry, immunofluorescence assay, and western blot in rats or FLSs.

FINDINGS: Administration of WISP1 knockdown improved joint damage and diminished synovial inflammation in CIA rats. WISP1 knockdown restrained TNF-α-induced cell vitality, migration, and invasion in FLSs. In CIA rats and TNFα-induced FLSs, WISP1 knockdown reduced the secretion of inflammatory factors and restrained NLRP3 inflammasome activation.

INTERPRETATION: WISP1 knockdown effectively inhibited NLRP3 inflammasome activation and inflammatory factors levels.

PMID:39938456 | DOI:10.1016/j.molimm.2025.02.004