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AB0108 Resveratrol Inhibits Canonical Wnt Signaling and Ameliorates Experimental Arthritis
  1. S.S. Koca1,
  2. S. Yolbas1,
  3. A. Yildirim1,
  4. Z.B. Celik2,
  5. E.E. Onalan2,
  6. M. Akin3
  1. 1Department of Rheumatology, Faculty of Medicine, Firat University
  2. 2Department of of Medical Biology, Faculty of Medicine, Firat University
  3. 3Department of Pathology, Faculty of Medicine, Firat University, Elazig, Turkey

Abstract

Background Rheumatoid arthritis (RA) is an inflammatory joint disorder, the progression of which leads to the destruction of cartilage and bone. Wnt signaling pathway act several important biological functions, such as cell differentiation, embryonic development, limb development and joint formation. Accumulated evidence has suggested that this signaling pathway plays a key role in the FLS activation, bone resorption and joint destruction in RA.

Objectives The purpose of this study was to investigate the activity of Wnt/β-catenin pathway in collagen-induced arthritis (CIA) in rats, and to research the therapeutic effect of resveratrol in this arthritis model.

Methods Thirty Wistar albino female rats were randomized to 3 groups (n=10 in each group): Group-I as the control group, Group-II as the arthritis (sham) group, and Group-III as the Resveratrol group. Arthritis was induced by intradermal injection of chicken type II collagen combined with incomplete Freund's adjuvant. One day after the onset of arthritis, resveratrol (20 mg/kg/day) was given via oral gavage, until they were killed on day 29. Animals were sacrificed at the 15th day after the onset of arthritis. The paws of the rats were obtained for further analysis. Perisynovial inflammation and cartilage-bone destruction were determined histopathologically in the paws. Tissue Wnt-5a, axin-2, DKK1, mitogen-activated protein kinase (MAPK), Src tyrosine kinase and signal transducer and activator of transcription-3 (STAT3) mRNA expressions were determined by real-time polymerase chain reaction (RT-PCR).

Results Arthritis was clinically developed at 12 to 13 days after the injection of collagen (Fig. 1a). The 29th day scores were decreased in the paricalcitol and pyrvinium groups compared to the own 13th day score (p<0.05 for both), while it was increased in the sham group (p<0.05). Histopathological analysis demonstrated the extensive perisynovial inflammation and marked cartilage-bone destruction in sham group rats. Resveratrol treatment decreased the perisynovial inflammation and cartilage-bone destruction in the paws. Moreover, the tissue mRNA expressions of Wnt5a (11 folds), axin-2 (22 folds) and DKK1 (3 folds) were increased in the sham group compared to the control group (Fig. 1b-d). However, resveratrol treatment decreased their expressions.

Figure 1.

Assessments of daily arthritis score (a) and the tissue mRNA expressions of Wnt5 (b), axin 2 (c) and DKK1 (d) in the all study groups.

Conclusions The present study shows that Wnt signaling pathway is active in CIA model. Resveratrol inhibits Wnt pathway and ameliorates CIA.

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  3. Kotha A, et al. Mol Cancer Ther. 2006;5(3):621–9.

  4. Zhong LX, et al. J Ovarian Res. 2015;8:25.

Acknowledgement None

Disclosure of Interest None declared

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