PDK1 promotes apoptosis of chondrocytes via modulating MAPK pathway in osteoarthritis |
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Authors: | Qingtian Ge Hailin Wang Xinbao Xu Libin Xu Leilei Zhai Ran Tao |
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Affiliation: | 1. Department of Orthopaedics, Affiliated Hospital of Nantong University, Nantong University, Nantong 226001, China;2. Department of Orthopaedics, The people Hospital of Jingjiang, Jingjiang 214500, China |
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Abstract: | 3-Phosphoinositide dependent protein kinase-1 (PDK1), a serine threonine kinase, belongs to the AGC kinase family and is associated with apoptosis. The aim of this study was to investigate the expression of PDK1 (3-Phosphoinositide dependent protein kinase-1) in articular cartilage with osteoarthritis (OA) and to analyze the relationship between PDK1 and chondrocyte apoptosis. Immunohistochemistry and RT-PCR analysis showed that the expression of PDK1 in articular cartilage of OA patients and healthy controls. IL-1β-stimulated SW1353 cells were used to imitate the OA-like chondrocyte injury in vitro, and IL-1β-induced the expression of PDK1, apoptotic markers(PARP, caspase-3), and phosphorylated p38 were detected by Western blot. The co-localization of PDK1 and Cleaved-caspase3 was confirmed through immunofluorescence. Knocking down PDK1 expression through PDK1 siRNA. Western blot was performed to detect the knockdown efficiency of PDK1 and the impact of PDK1 knockout on IL-1β-induced expression of apoptotic markers and phosphorylated p38 in SW1353 cells. Flow Cytometry-Based Annexin V/PI Staining was used to exam chondrocyte apoptosis. Our experimental results suggested that PDK1 may promote chondrocyte apoptosis in OA via p38 MAPK signaling pathway. |
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Keywords: | PDK1 Osteoarthritis apoptosis Mapk Interleukin-1&β |
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