Biao Zhou1,2, Lin-Hui Li1, Li-Ming Tan3,4, Wen-Bing Luo5,6, Hui Xiong6, Xiao-Long Lu7, Dan Liu8, Wang-Yang Li6, Yu-Xing Guo6, Zhi Tang6, Li-Guo Zhu9. 1. Department of Orthopedics, Wangjing Hospital of Chinese Academy of Chinese Medical Science, Beijing, China. 2. Department of Orthopedics, Xiangtan Hospital Affiliated to Nanhua University, Xiangtan, China. 3. Department of Orthopedics, The Fourth Hospital of Changsha, Changsha, China. 4. Department of Orthopedics, Changsha Hospital of Tranditional Chinese Medicine, Changsha, China. 5. Department of Orthopedics, The Chinese Medicine Hospital of Linli County, Linli, China. 6. Department of Orthopedics, Hunan University of Chinese Medicine, Changsha, China. 7. Department of Orthopedics, The Second Affiliated Hospital of Hunan University of Chinese Medicine, Changsha, China. 8. Department of Rheumatology, The First Hospital of Hunan University of Chinese Medicine, Changsha, China. 9. Department of Orthopedics, Wangjing Hospital of Chinese Academy of Chinese Medical Science, Beijing, China, zhuliguow712@163.com.
Abstract
BACKGROUND: Osteoarthritis (OA) is the most common joint disorder characterized by degeneration of the articular cartilage and joint destruction with an associated risk of mobility disability in elderly people. Although a lot of achievements have been made, OA is still regarded as an incurable disease. Therefore, the pathological mechanisms and novel therapeutic strategies of OA need more investigation. METHODS: MTT assay was conducted to measure the viability of chondrocytes after LPS treatment. Cell apoptosis was analyzed by annexin V/propidium iodide labeling. ELISA was used to determine the concentrations of interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α in the culture supernatant of chondrocytes. The expression level of miR-155, IL-1β, FOXO3, TNF-α, IL-6, caspase-3, and caspase-9 in chondrocytes was analyzed by RT-qPCR or Western blot. RESULTS: We found that LPS led to inflammatory responses, cell apoptosis, and increased miR-155 expression in human articular chondrocytes. Tanshinone IIA could inhibit LPS-induced inflammation and cell apoptosis of chondrocytes via regulating the expression of miR-155 and FOXO3. miR-155 directly targeted the 3'-UTR of FOXO3 to regulate its expression. CONCLUSIONS: Taken together, our data suggest tanshinone IIA ameliorates inflammation response in OA via inhibition of the miR-155/FOXO3 axis, and provide some evidences that tanshinone IIA could be designed and developed as a new promising clinical therapeutic drug for OA patients.
BACKGROUND:Osteoarthritis (OA) is the most common joint disorder characterized by degeneration of the articular cartilage and joint destruction with an associated risk of mobility disability in elderly people. Although a lot of achievements have been made, OA is still regarded as an incurable disease. Therefore, the pathological mechanisms and novel therapeutic strategies of OA need more investigation. METHODS:MTT assay was conducted to measure the viability of chondrocytes after LPS treatment. Cell apoptosis was analyzed by annexin V/propidium iodide labeling. ELISA was used to determine the concentrations of interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α in the culture supernatant of chondrocytes. The expression level of miR-155, IL-1β, FOXO3, TNF-α, IL-6, caspase-3, and caspase-9 in chondrocytes was analyzed by RT-qPCR or Western blot. RESULTS: We found that LPS led to inflammatory responses, cell apoptosis, and increased miR-155 expression in human articular chondrocytes. Tanshinone IIA could inhibit LPS-induced inflammation and cell apoptosis of chondrocytes via regulating the expression of miR-155 and FOXO3. miR-155 directly targeted the 3'-UTR of FOXO3 to regulate its expression. CONCLUSIONS: Taken together, our data suggest tanshinone IIA ameliorates inflammation response in OA via inhibition of the miR-155/FOXO3 axis, and provide some evidences that tanshinone IIA could be designed and developed as a new promising clinical therapeutic drug for OA patients.