ABSTRACT
Objective To establish the models with human rheumatoid arthritis (RA) synovial fibroblasts (RASFs)-cartilage-severe combined immune deficient (SCID) mice for the study of the RASFs in the pathogenesis of RA.Methods The 4th passage RASFs were marked with 5-bromodexyuridine (5-Brdu)and injected into a cavity of inert sterile gel sponge,then with the normal human cartilage co-implanted in the back subcutaneously of SCID mice to set up a novel model of RA.Osteoarthritis synovial fibroblasts (OASFs)were injected as control group.Thirty days after the surgery,the mice were killed,the grafts and the knee joints were proceed with histological study and immunohistochemistry to detect the expression of 5-Brdu and Vimentin in synoviocytes.The serum level of interleukin (IL)-6 and matrix metalloproteinase (MMP)-3 were detected with enzyme-linked immunosorbent assay (ELISA).Results Twenty-three mice survived except for one mouse in the RASFs group died of anesthesia.① Only in one case in the RASFs group,the IL-6 was detected,the others were unable to be detected.The MMP-3 in the OASFs group was (40±17) pg/ml,but in RASFs group only one case was detected.② There were 4 and 3 implanted cartilages loss in the RASFs group and OASFs group respectively.The histological scores of cartilage invasion by synoviocytes and cartilage degradation in grafts were higher in RASFs groups than in OASFs groups (0.6±0.7 vs 0.3±0.5,2.3±0.8 vs 1.7±1.0 respectively).③ The histological scores of synovial hyperplasia and cartilage invasion in the knee joints was significantly higher in the RASFs group than in the OASFs group (3.1±0.8 vs 1.7±1.0,P＜0.01,1.6±1.7 vs 0.6±1.4,P＜0.05 respectively).④ During the grafts,a lot of 5-Brdu and Vimentin markers positive synovio-cytes were found in the mice subcutaneous tissue,but manipulus positive synoviocytes were found on the area of cartilage invasion in both groups.In knee joints,single positive synoviocytes could be detected in bone marrow and hyperplasic area of the synovial tissue in both groups.Conclusion The isolated RASFs can survival and have the ability to invade and degrade the cartilage in vivo without the limitation of immunity induced inflammations,and can also migrate to the synovial joints in distance and induce arthritis.