Effect of Abatacept on chronic inflammation and bone erosion in rheumatoid arthritis
Objective To observe the effects of Abatacept on chronic inflammation and bone erosion in rheumatoid arthritis(RA)via a mouse model of collagen-induced arthritis(CIA).Methods Sixty BALB/c female mice were divided into the normal group,CIA model group,methotrexate(MTX)-positive control group,and Abatacept low-,medium-,and high-dose groups according to the simple random grouping method,with 10 mice in each group.In addition to the normal group,the RA model was established by collagen induction in the remaining 5 groups.After CIA modeling,the mice were administered the equivalent dose of CIA according to the routine clinical dose for adult patients.The MTX positive control group was administered MTX tablets by gavage once per week.Abatacept low-,medium-and high-dose groups were intraperitoneally injected with the corresponding dose of Abatacept injection,200 μL,once a week,respectively.The normal group and CIA model group were injected intraperitoneally with 0.9％sodium chloride solution,200 μL,once a week.The arthritis index scores of each group were compared,and the expressions of serum TNF-α,IL-6 and matrix metalloproteinase(MMP)were detected by enzyme-linked immunosorbent assay,and the morphology of the synovial membrane of the ankle joint and the degree of inflammatory cell infiltration were observed by HE staining method;The expressions of TNF-α,osteopontin(OPN),NF-κB,and receptor activator of NF-κB ligand(RANKL)of the ankle joint were detected by immunohistochemistry method.Results Compared with the normal group,after modeling,the ankle joints of mice in all other groups were swollen,with severely limited mobility and elevated arthritis index scores;serum IL-6,TNF-α,MMP-2,and MMP-9 levels were elevated(all P＜0.01);synovial hyperplasia and obvious inflammatory infiltration were observed in the ankle joints,and the expressions of TNF-α,OPN,NF-κB,and RANKL were all elevated.Compared with the CIA model group,the ankle joint swelling was reduced in the MTX positive control group and the Abatacept medium-and high-dose groups,the arthritis index scores were all also reduced(P＜0.05),so were the expression levels of serum IL-6,TNF-α,MMP-2,and MMP-9(all P＜0.01);synovial hyperplasia and inflammatory infiltration of the ankle joints were all significantly reduced,and the expression levels of TNF-α,OPN,NF-κB,and RANKL were all decreased.Conclusion Abatacept significantly attenuated joint inflammatory responses of CIA mice and inhibited their synovial proliferation and bone destruction.
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