Abstract
Synovial hyperplasia is the main cause of chronic rheumatoid arthritis (RA), but the mechanism of synovial hyperplasia is still unclear. Etodolac (ETD) is a selective COX-2 inhibitor for relieving pain and stiffness in RA, but the disease modifying effect is still lack of evidence. Proteomics method was used to study the differential proteome of synovial tissue in collagen induced arthritis (CIA) in rats. With the help of STRING analysis, the upregulated proteins enriched in the cluster of complement and coagulation cascades and platelet degranulation were highlighted, these proteins with fibrogenic factors Lum, CIV, CXI and Tgfbi participated in the synovial inflammation, fibrosis and hyperplasia in CIA. Based on KOG function class analysis, the proteins involved in the events of the central dogma was explored. They might be hyperplasia related proteins for most of them are related to the proliferation of cancer. ETD significantly attenuated synovial inflammation, fibrosis and hyperplasia in CIA rats by downregulating these proteins. Several proteins have not been observed in RA so far, such as Tmsb4x, Pura, Nfic, Ruvbl1, Snrpd3, U2af2, Srrm2, Srsf7, Elavl1, Hnrnph1, Wars, Yars, Bzw2, Mcts1, Eif4b, Ctsh, Lamp1, Dpp7, Ptges3, Cdc37 and Septin9, they might be potentials targets for RA. Blood biochemistry tests showed the safety of 7 months use of ETD on rats. In conclusion, present study displayed a comprehensive mechanism of synovial hyperplasia in CIA rats, on this basis, the clinical value of ETD in the treatment of RA was well confirmed.
Highlights
Synovial hyperplasia is the main cause of chronic rheumatoid arthritis (RA), but the mechanism of synovial hyperplasia is still unclear
ETD significantly modified the symptoms of collagen induced arthritis (CIA) rats Rats in the control group demonstrated no gross signs of arthritis
Immunization with collagen was associated with expected increases in right heel width, and the swelling degree reached its peak at 30 days after immunization
Summary
Synovial hyperplasia is the main cause of chronic rheumatoid arthritis (RA), but the mechanism of synovial hyperplasia is still unclear. Present study displayed a comprehensive mechanism of synovial hyperplasia in CIA rats, on this basis, the clinical value of ETD in the treatment of RA was well confirmed. Glucocorticoids and non-steroidal anti-inflammatory drugs (NSAIDs) were used for the treatment of RA, mainly for the control of pain and inflammation, disease modifying anti rheumatic drugs, as the first-line drugs for the new diagnosis of RA, and biotherapy, which were used to target and inhibit (2021) 2:33 specific molecules of immune and inflammatory response [2]. ETD had anti-inflammatory effects with better gastric safety on adjuvant arthritis and normal rats than that of non-selective NSAIDs diclofenac sodium and indomethacin [6]. The mechanisms hidden behind the protective effects of ETD on RA were further investigated
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