Genistein promotes cartilage repair and inhibits synovial inflammatory response after anterior cruciate ligament transection in rats by regulating the Wnt/β-catenin axis.

Autor: Wang J; Trauma department of orthopedics, Yantaishan Hospital, 10087 Keji Avenue, Laishan District, Yantai, Shandong, China. wangjianhang_yt@163.com., Liu Y; Trauma department of orthopedics, Yantaishan Hospital, 10087 Keji Avenue, Laishan District, Yantai, Shandong, China., Jing Y; Trauma department of orthopedics, Yantaishan Hospital, 10087 Keji Avenue, Laishan District, Yantai, Shandong, China., Fu M; Trauma department of orthopedics, Yantaishan Hospital, 10087 Keji Avenue, Laishan District, Yantai, Shandong, China.
Jazyk: angličtina
Zdroj: Naunyn-Schmiedeberg's archives of pharmacology [Naunyn Schmiedebergs Arch Pharmacol] 2024 Oct; Vol. 397 (10), pp. 8053-8068. Date of Electronic Publication: 2024 May 22.
DOI: 10.1007/s00210-024-03168-7
Abstrakt: To confirm the protective mechanism of genistein on osteoarthritis (OA). Firstly, we constructed an anterior cruciate ligament transection (ACLT) rat model and administered two doses of genistein via gavage. The effects of the drug on cartilage damage repair and synovitis in OA rats were evaluated through pain-related behavioral assessments, pathological staining, detection of inflammatory factors, and western blot analysis. Secondly, we constructed IL-1-induced chondrocytes and synovial fibroblast models, co-incubated them with genistein, and evaluated the protective effects of genistein on both types of cells through cell apoptosis and cytoskeleton staining. To verify the role of this pathway, we applied the GSK3β inhibitor TWS119 and the Wnt/β-catenin inhibitor XAV939 to ACLT rats and two types of cells to analyze the potential mechanism of genistein's action on OA. Our results confirmed the protective effect of genistein on joint cartilage injury in ACLT rats and its alleviating effect on synovitis. The results of cell experiments showed that genistein can protect IL-1β-induced chondrocytes and synovial fibroblasts, inhibit IL-1β-induced cell apoptosis, increase the fluorescence intensity of F-actin, and inhibit inflammatory response. The results of in vivo and in vitro mechanism studies indicated that TWS119 and XAV939 can attenuate the protective effects of genistein on OA rats and IL-1-induced cell damage. Our research confirmed that genistein may be an effective drug for treating osteoarthritis. Furthermore, we discussed and confirmed that the GSK3β/Wnt/β-catenin axis serves as a downstream signaling pathway of genistein, providing theoretical support for its application.
(© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)
Databáze: MEDLINE
Externí odkaz: