Osteoarthritis (OA) and rheumatoid arthritis (RA) are two of the most common types of arthritis. Both are characterized by the infiltration of a number of proinflammatory cytokines into the joint microenvironment. miRNAs play critical roles in the disease processes of arthritic disorders. However, little is known about the effects of miRNAs on critical inflammatory cytokine production with OA and RA progression. Here, we found higher levels of proinflammatory cytokines including interleukin 1 beta (IL-1β), interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF-α) in human OA and RA synovial fibroblasts (SFs) compared with normal SFs. Searches of open-source microRNA (miRNA) software determined that miR-let-7c-5p and miR-149-5p interfere with IL-1β, IL-6 and TNF-α transcription; levels of all three proinflammatory cytokines were lower in human OA and RA patients compared with normal controls. Anti-inflammatory agents dexamethasone, celecoxib and indomethacin reduced proinflammatory cytokine production by promoting the expression of miR-let-7c-5p and miR-149-5p. Similarly, ibuprofen and methotrexate also enhanced miR-let-7c-5p and miR-149-5p expression in human SFs. The evidence suggests that increasing miR-let-7c-5p and miR-149-5p expression is a novel strategy for OA and RA.
Background Osteoarthritis (OA) is the most common joint disease, especially affecting the knee joint. Etoricoxib, a highly selective cyclooxygenase (COX)‐2 inhibitor which can reduce postoperative pain after orthopaedic surgery. The aim of this study was to investigate the effects of oral etoricoxib on the development of OA and to examine concomitant changes in the nociceptive behaviour of rats. Method OA was induced in wistar rats by anterior cruciate ligament transection (ACLT) of the right knee. The ACLT + etoricoxib groups received 6.7 or 33.3 mg/kg of oral etoricoxib three times a week for 12 consecutive weeks, starting at week 8 after ACLT. Nociceptive behaviours and changes in knee joint width during OA development were analyzed. Histopathological studies were then performed on the cartilage. Immunohistochemical analysis was performed to examine the effect of etoricoxib on the expression of transforming growth factor‐beta (TGF‐β) and nerve growth factor (NGF) in articular cartilage chondrocytes. Results OA rats receiving etoricoxib showed a significantly lower degree of cartilage degeneration than the rats receiving placebo. Nociceptive behaviour studies showed significant improvement in the ACLT + etoricoxib groups compared to that in the ACLT group. Moreover, etoricoxib attenuated NGF expression, but increased TGF‐β expression, in OA‐affected cartilage. Conclusions Oral etoricoxib in a rat OA model (a) attenuates the development of OA, (b) concomitantly reduces nociception, and (c) modulates chondrocyte metabolism, possibly by inhibiting NGF expression and increasing TGF‐β expression. Significance Oral administration of etoricoxib can attenuate the development of OA, with an associated attenuation of nociceptive behaviour in an experimental rat OA model. Moreover, etoricoxib attenuated NGF expression, but enhanced TGF‐β expression in OA‐affected chondrocytes. These findings may pave the way for further investigations of etoricoxib as a potential therapeutic target for the treatment of the inflammatory component in OA.
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