Ginsenoside compound K alleviates osteoarthritis by inhibiting NLRP3‑mediated pyroptosis

Li,Yuguo; Wu,Jiang; Zhuo,Naiqiang

doi:10.3892/etm.2023.12105

Ginsenoside compound K alleviates osteoarthritis by inhibiting NLRP3‑mediated pyroptosis

Authors:
- Yuguo Li
- Jiang Wu
- Naiqiang Zhuo
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Affiliations: School of Clinical Medicine, Southwest Medical University, Luzhou, Sichuan 646000, P.R. China, School of Clinical Medicine, Guizhou Medical University, Guiyang, Guizhou 550025, P.R. China, Department of Orthopedics, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan 646000, P.R. China
Published online on: July 10, 2023 https://doi.org/10.3892/etm.2023.12105
Article Number: 406
Copyright: © Li et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Ginsenoside compound K (GCK) has been previously reported to be a potent antiarthritic and bone‑protective agent. Therefore, the present study aimed to explore the potential effects of GCK on osteoarthritis and its regulatory effects on the pyroptosis of chondrocytes. Primary mouse chondrocytes (PMCs) were used for in vitro analysis. ELISA assays revealed that compared with the untreated cells, TNF‑α induced a significant increase in IL‑6, MMP13, A disintegrin and metalloproteinase with thrombospondin motifs 5 and MMP3 expression but induced a significant decrease in aggrecan and collagen II expression. By contrast, GCK reversed the aforementioned alterations in a dose‑dependent manner. Experimental osteoarthritis was subsequently induced in mice through transection of the medial meniscotibial ligament and medial collateral ligament in the right knee [destabilization of the medial meniscus (DMM) mice]. GCK was found to reduce cartilage degradation in vivo in DMM mice, which was assessed using the Osteoarthritis Research Society International (OARSI) score, collagen II and MMP13 expression. Cartilage degradation is associated with higher OARSI score, decreased collagen II and increased MMP13 expression. In PMCs, TNF‑α treatment stimulated an increase in the expression of NLR family pyrin domain containing 3 (NLRP3), Gasdermin D‑N terminal (GSDMD‑NT), cleaved caspase‑1 and mature IL‑1β, markers that indicate the occurrence of pyroptosis. However, GCK treatment suppressed the increase of the aforementioned proteins in a dose‑dependent manner. Immunohistochemistry staining of the knee joint tissue sections from the DMM mice confirmed that GCK attenuated the NLRP3 and GSDMD‑NT expression that was induced by DMM surgery. In conclusion, the present study revealed that GCK can reduce cartilage degradation in an osteoarthritis model by inhibiting the NLRP3‑inflammasome activation and subsequent pyroptosis.

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