Artemisinin relieves osteoarthritis by activating mitochondrial autophagy through reducing TNFSF11 expression and inhibiting PI3K/AKT/mTOR signaling in cartilage

被引:74
|
作者
Li, Jin [1 ]
Jiang, Mengqing [2 ]
Yu, Zhentang [3 ]
Xiong, Chenwei [3 ]
Pan, Jieen [1 ]
Cai, Zhenhai [1 ]
Xu, Nanwei [3 ]
Zhou, Xindie [3 ]
Huang, Yong [3 ]
Yang, Zhicheng [3 ]
机构
[1] Jiaxing Univ, Affiliated Hosp 2, Dept Orthoped Surg, Jiaxing 314000, Peoples R China
[2] Jiaxing Univ, Affiliated Hosp 2, Dept Pharm, Jiaxing 314000, Peoples R China
[3] Nanjing Med Univ, Affiliated Changzhou 2 Peoples Hosp, Dept Orthoped, Changzhou 213000, Peoples R China
关键词
Artemisinin; PI3K; AKT signaling pathway; Autophagy; TNFSF11; Mitochondria; Osteoarthritis; IN-VITRO; SUPPRESSING OSTEOCLASTOGENESIS; PATHWAY; RANKL; CHONDROCYTES; OSTEOPOROSIS; ARTESUNATE; APOPTOSIS; INTERLEUKIN-1-BETA; PROLIFERATION;
D O I
10.1186/s11658-022-00365-1
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Osteoarthritis (OA) is a widespread chronic degenerative joint disease characterized by the degeneration of articular cartilage or inflamed joints. Our findings indicated that treatment with artemisinin (AT) downregulates the protein levels of MMP3, MMP13, and ADAMTS5, which are cartilage degradation-related proteins in OA, and inhibits the expression of inflammatory factors in interleukin-1 beta (IL-1 beta)-stimulated chondrocytes. However, the mechanism of the role of AT in OA remains unclear. Here, we performed gene sequencing and bioinformatics analysis in control, OA, and OA + AT groups to demonstrate that several mRNA candidates were enriched in the PI3K/AKT/mTOR signaling pathway, and TNFSF11 was significantly downregulated after AT treatment. TNFSF11 was downregulated in the OA + AT group, whereas it was upregulated in rat OA tissues and OA chondrocytes. Therefore, we confirmed that TNFSF11 was the target gene of AT. In addition, our study revealed that AT relieved cartilage degradation and defection by activating mitochondrial autophagy via inhibiting the PI3K/AKT/mTOR signaling pathway in IL-1 beta-induced chondrocytes. Furthermore, an OA model was established in rats with medial meniscus destabilization. Injecting AT into the knee joints of OA rat alleviated surgical resection-induced cartilage destruction. Thus, these findings revealed that AT relieves OA by activating mitochondrial autophagy by reducing TNFSF11 expression and inhibiting PI3K/AKT/mTOR signaling.
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页数:19
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