Abstract
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.
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This work was supported by the 2023 Yantai Science and Technology Innovation Plan (grant number 2023YD019).
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All authors conceived and designed the research. JW: material preparation, data curation, formal analysis, funding acquisition, and writing of the original draft. YL: material preparation, data curation and formal analysis, investigation, and methodology. MF: material preparation, investigation, and methodology. YJ: project administration and resources. All authors commented on previous versions of the manuscript. All authors read and approved the final manuscript. The authors declare that all data were generated in-house and that no paper mill was used.
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The animal experiments were approved by the Institutional Animal Care and Use Committee of Yantaishan Hospital (ethical approval number: 2024004). All protocols were carried out in accordance with the European Union regulations for the handling and use of laboratory animals and are reported following the ARRIVE guidelines for reporting experiments involving animals.
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Wang, J., Liu, Y., Jing, Y. et al. Genistein promotes cartilage repair and inhibits synovial inflammatory response after anterior cruciate ligament transection in rats by regulating the Wnt/β-catenin axis. Naunyn-Schmiedeberg's Arch Pharmacol (2024). https://doi.org/10.1007/s00210-024-03168-7
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DOI: https://doi.org/10.1007/s00210-024-03168-7