Background/Purpose: Rheumatoid arthritis (RA) is an inflammatory joint disorder, the progression of which leads to the destruction of cartilage and bone. Fibroblast-like synoviocytes (FLS) display an important role in the pathogenesis of RA. 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. The purpose of this study was to investigate the therapeutic effect of lapatinib on collagen-induced arthritis (CIA) in rats.

Methods: Forty Wistar albino female rats were randomized to 4 groups (n=10 in each group): Group-I as the control group, Group-II as the arthritis (sham) group, Group-III as the Paricalcitol group and Group-IV as the Pyrvinium group were assigned. Arthritis was induced by intradermal injection of chicken type II collagen combined with incomplete Freund’s adjuvant. One day after the onset of arthritis, paricalcitol (0.3 μg/kg/day) was injected subcutaneously, and pyrvinium (5 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 axin-2, Wnt-5a and DKK1 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 (Figure). 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. Paricalcitol and pyrvinium treatments decreased the perisynovial inflammation and cartilage-bone destruction in the paws. Moreover, the tissue mRNA expressions of axin-2 (22 folds), Wnt5a (11 folds) and DKK1 (3 folds) were increased in the sham group compared to the control group. Their mRNA expressions in paricalcitol and pyrvinium groups were similar in the control group.

Conclusion: The present study shows that Wnt signaling pathway is active in CIA model. Moreover, paricalcitol and pyrvinium those are inhibit Wnt pathway ameliorate CIA. These agents may be candidate to further research in human RA.

References:

1. Miao CG, et al. Cell Signal. 2013;25(10):2069-78.

2. Saraswati S, et al. Wound Repair Regen. 2012;20(2):185-93.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/the-inhibition-of-wntbeta-catenin-signaling-pathway-via-paricalcitol-and-pyrvinium-ameliorates-experimental-arthritis/