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death-associated -protein kinase 1 (DAPK1), IL-1 β, inflammation, osteoarthritis (OA), P38 MAPK pathway
Objective: To reveal the possible effects of death-associated protein kinase 1 (DAPK1) on the progression of osteoarthritis (OA) and the potential underlying mechanism.
Methods: The expression of DAPK1 in OA and normal samples and interleukin (IL)-1β-stimulated chondrocytes was analyzed by quantitative real-time polymerase chain reaction and Immunoblot assay. Cell viability, proliferation, and apoptosis in DAPK1-knockdown cells stimulated with IL-1β were detected by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) solution, 5-ethynyl-2β-deoxyuridine staining and flow cytometry. The chondrocyte degradation and inflammatory response in IL-1β-induced chondrocytes were investigated by Immunoblot analysis and enzyme-linked-immunosorbent serologic assay. In addition, the effect of DAPK1 on p38 mitogen-activated protein kinase (MAPK) activation was analyzed by immunoblot assay.
Results: This study revealed that DAPK1 was highly expressed in OA patients and IL-1β-induced chondrocytes. Down-regulation of DAPK1 enhanced IL-1β-induced chondrocyte proliferation. DAPK1 knockdown inhibited IL-1β-induced chondrocyte degradation. In addition, DAPK1 depletion inhibited IL-1β-induced chondrocyte inflammation. Mechanically, it was revealed that down--regulation of DAPK1 could inhibit the p38 MAPK pathway, and therefore affected progression of OA.
Conclusion: DAPK1 knockdown attenuates IL-1β-induced extracellular matrix degradation and inflammatory response in OA chondrocytes by regulating the p38 MAPK pathway.
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