Research on the differentiation direction of synovial cells induced by IL-17RA specific nucleic acid aptamer in experimental arthritis mice
Objective To detect the impact of interleukin-17 receptor A(IL-17RA)specific nucleic acid aptamer on the phenotype and function of synovial macrophages(Mφ)and fibroblast-like synoviocytes(FLS)in experimental arthritis mice.Methods The medial meniscus of the knee joint in mice was surgically removed to establish a mouse model of traumatic experimental arthritis,and the impacts of IL-17RA specific nucleic acid aptamer RA10-6 on the phenotype and function of Mφ and FLS in vitro were detected.Results After a certain dose of RA10-6 was administered to mouse synovial Mφ,the expression level of CD206 molecules in cell differentiation clusters was increased,while the level of CD16/32 molecules was reduced,with statistically significant differences(P<0.05).It could promote the enzymatic activity of human arginase-1 in Mφ and inhibit the activity of cell-inducible nitric oxide synthase to a certain extent.However,the impacts on CD163 and DECTIN-1 molecules were not obvious,without statistically significant differences(P>0.05).Under the function of RA10-6,the levels of interleukin-10 in mouse synovial Mφ significantly increased.There was a certain degree of increase in transforming growth factor-β,but the increase was not as obvious as interleukin-10.Meanwhile,interleukin-12 was significantly reduced.After RA10-6 acted on mouse synovial fibroblasts,the expression level of CD248 molecule could be increased,with statistically significant differences(P<0.05).However,the impact on CD90.5 and vascular cell adhesion molecule-1 was not obvious,without statistically significant differences(P>0.05).The aptamer had no obvious impact on the activity of cell uridine diphosphate glucose dehydrogenase,without statistically significant difference(P>0.05).However,it had a promoting function on the expression of fibronectin.Under the function of RA10-6,there were no statistically significant differences in the impacts of cytokines such as interleukin-6,chemokine ligand 2 and tumor necrosis factor-α on mouse synovial fibroblasts(P>0.05).Conclusion IL-17RA specific nucleic acid aptamer RA10-6 can reduce the expression of inflammatory cytokines and inhibit the progress of arthritis by inducing phenotypic changes of synovial Mφ.
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