The Treatment Of ⁹⁹Tc-MDP In Collagen-induced Arthritis Rats And Effect On Wnt Signaling Pathway

Objective:To determine the jionts protection of 99Tc-MDP in collagen-induced arthritis rats model and its effect on Wnt signaling pathway, and explore the possible treatment mechanism of 99Tc-MDP in rheumatoid arthritis(RA).Methods:Selected 6 SD rats randomly as normal group, the others were immunized with an emulsion of collagen.18 CIA rats were randomly divided into 3 groups:Normal group and CIA model group receiving saline water, low dose 99Tc-MDP treatment group(2mg/kg·d) and high dose 99Tc-MDP treatment group(4mg/kg·d). totall 14days, Paw inflammation was assessed by arthritis index. Lesions of bone and cartilage were evaluated on the basis of histological change in ankle joint, radiographic analysis in hind paw with X ray by Larsen score. All rats were killed on day 29, immunohistochemical detection of joints local Wnt5a,β-catenin, Lrp5 expression, The expression of Wnt1,Wnt5a,β-catenin mRNA in synovium was analyzed by real time-PCR.Results:1. The arthritis index and mean radiographic scores were significantly lower in 99Tc-MDP treatment groups than in CIA model group. Histological analysis confirmed the suppression of joint inflammation and showed prevention of cartilage and bone destruction after treatment of 99Tc-MDP.2. Both 99Tc-MDP treatment groups expression ofβ-catenin increased significantly contrast to the model, but there is not different between both treatment groups.3. normal group rats joints areas show fewer Wnt5a positive cells, the expression is also lower in model group and of 99Tc-MDP group, there is no significant difference among the four groups. Compared with normal rats, the positive expression of Lrp5 is visible in model group bone areas, but there is no significant difference. Lrp5 showed no significant difference in 99Tc-MDP group contrast to model group.4. Compared with the normal group, the lever of Wnt1, Wnt5a,β-catenin mRNA are not different in Synovial tissue among model group and both 99Tc-MDP groups, show no significant difference.Conclusion:1.99Tc-MDP offered a significant joint protection in CIA rats.2.The effects of 99Tc-MDP on the CIA rats may be related to its regulation of (3-catenin protein in Wnt signaling pathway. It may be one of the effective mechanism in the treatment of RA.3. the joint protection of99Tc-MDP is independent with the expression of Wntl,Wnt5a and Lrp5 in CIA rats.