The COX-2 inhibitor etoricoxib reduces experimental osteoarthritis and nociception in rats: The roles of TGF-β1 and NGF expressions in chondrocytes

Zhi Hong Wen, Yen You Lin, Yi Chen Chang, Chi Chieh Tang, Shih Peng Hsieh, Hsin Pai Lee, Chun Sung Sung, Wu Fu Chen, Chian Her Lee, Yen Hsuan Jean

研究成果: 雜誌貢獻文章同行評審

3 引文 斯高帕斯(Scopus)

摘要

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.
原文英語
頁(從 - 到)209-222
頁數14
期刊European Journal of Pain (United Kingdom)
24
發行號1
DOIs
出版狀態已發佈 - 一月 1 2020

ASJC Scopus subject areas

  • 麻醉與疼痛醫學

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