Artesunate alleviates interleukin‑1β‑induced inflammatory response and apoptosis by inhibiting the NF‑κB signaling pathway in chondrocyte‑like ATDC5 cells, and delays the progression of osteoarthritis in a mouse model

Li,Yicheng; Mu,Wenbo; Ren,Jiangdong; Wuermanbieke,Shalitanati; Wahafu,Tuerhongjiang; Ji,Baochao; Ma,Hairong; Amat,Abdusami; Zhang,Keyuan; Cao,Li

doi:10.3892/ijmm.2019.4290

Artesunate alleviates interleukin‑1β‑induced inflammatory response and apoptosis by inhibiting the NF‑κB signaling pathway in chondrocyte‑like ATDC5 cells, and delays the progression of osteoarthritis in a mouse model

Authors:
- Yicheng Li
- Wenbo Mu
- Jiangdong Ren
- Shalitanati Wuermanbieke
- Tuerhongjiang Wahafu
- Baochao Ji
- Hairong Ma
- Abdusami Amat
- Keyuan Zhang
- Li Cao
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Affiliations: Department of Orthopedics, First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang 830054, P.R. China, State Key Laboratory of Pathogenesis, Prevention and Treatment of High Incidence Diseases in Central Asian Xinjiang Key Laboratory of Echinococcosis, Clinical Medical Research Institute, First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang 830054, P.R. China
Published online on: July 26, 2019 https://doi.org/10.3892/ijmm.2019.4290
Pages: 1541-1551

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Abstract

Osteoarthritis (OA) is a progressive and degenerative joint disorder that is highly prevalent worldwide and for which there is currently no effective medical therapy. Artesunate (ART), a natural compound used to treat malaria, possesses diverse biological properties, including the regulation of inflammation and apoptosis in various cells; however, its role in OA remains unclear. The aim of the present study was to investigate the effects of ART on interleukin (IL)‑1β‑induced chondrocyte‑like ATDC5 cells and in an OA mouse model. The results revealed that ART dose‑dependently relieved the inhibitory effect of IL‑1β on cell viability. Moreover, ART significantly reduced the overexpression of matrix metalloproteinase (MMP)‑3, MMP‑13, a disintegrin and metalloproteinase with thrombospondin motifs‑5 and cyclooxygenase‑2 at both the gene and protein levels in chondrocyte‑like ATDC5 cells stimulated by IL‑1β. Furthermore, ART decreased the expression of pro‑apoptotic Bax, cleaved caspase‑3 and cleaved caspase‑7 in a dose‑dependent manner, and increased the expression of the anti‑apoptotic factor Bcl‑2. These changes were mediated by the inhibitory effect of ART on the nuclear factor‑κB signaling pathway, defined as repression of the phosphorylation of IκBα and p65, and improved redistribution of p65. Additionally, ART blocked the advancement of the calcified cartilage zone and the loss of proteoglycan, and lowered histological scoring of OA in a mouse model. Taken together, these results indicate that ART may be of value as a therapeutic agent for OA.

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