2. Academic Validation
  3. Wilforine inhibits rheumatoid arthritis pathology through the Wnt11/β-catenin signaling pathway axis

Wilforine inhibits rheumatoid arthritis pathology through the Wnt11/β-catenin signaling pathway axis

  • Arthritis Res Ther. 2023 Dec 14;25(1):243. doi: 10.1186/s13075-023-03224-2.
Yurong Huang 1,  Yanhui Peng 1,  Hui Li 1,  Chen Li 1,  Yajie Wu 1,  Xiaomei Wang 2,  Jun Chang 3 4,  Chenggui Miao 5
Affiliations

Affiliations

  • 1 Department of Pharmacology, School of Integrated Chinese and Western Medicine, Anhui University of Chinese Medicine, Hefei, 230012, Anhui Province, China.
  • 2 Department of Humanistic Nursing, School of Nursing, Anhui University of Chinese Medicine, Hefei, China. [email protected].
  • 3 Department of Orthopaedics, the First Affiliated Hospital, Anhui Medical University, Hefei, 230032, China. [email protected].
  • 4 Anhui Public Health Clinical Center, Hefei, China. [email protected].
  • 5 Department of Pharmacology, School of Integrated Chinese and Western Medicine, Anhui University of Chinese Medicine, Hefei, 230012, Anhui Province, China. [email protected].
PMID: 38098062 DOI: 10.1186/s13075-023-03224-2
Abstract

Background: Wilforine (WFR) is a monomeric compound of the anti-RA plant Tripterygium wilfordii Hook. f. (TwHF). Whether WFR has anti-RA effect, its molecular mechanism has not been elucidated.

Aim of the study: Our study aims to clarify how WFR inhibits fibroblast-like synovial cells (FLS) activation and improves RA through Wnt11 action on the Wnt11/β-catenin signaling pathway.

Methods: The therapeutic effect of WFR on collagen-induced arthritis (CIA) rats was evaluated using methods such as rat arthritis score. The inhibitory effects and signaling pathways of WFR on the proliferation and inflammatory response of CIA FLS and RA FLS were studied using ELISA, CCK-8, RT-qPCR, Western blot, and immunofluorescence methods.

Results: WFR could effectively alleviate the arthritis symptoms of CIA rats; reduce the levels of IL-6, IL-1β, and TNF-α in the peripheral blood of CIA rats; and inhibit the expression of MMP3 and fibronectin. The data showed that WFR has a significant inhibitory effect on FLS proliferation. Furthermore, WFR inhibited the activation of Wnt/β-catenin signaling pathway and decreased the expression of Wnt11, β-catenin, CCND1, GSK-3β, and c-Myc, while the effects of WFR were reversed after overexpression of Wnt11.

Conclusions: WFR improves RA by inhibiting the Wnt11/β-catenin signaling pathway, and Wnt11 is the direct target of WFR. This study provides a new molecular mechanism for WFR to improve RA and contributes to the clinical promotion of WFR.

Keywords

Fibroblast-like synoviocytes; Rheumatoid arthritis; Tripterygium wilfordii Hook. f.; Wilforine; Wnt11/β-catenin signaling pathway.

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