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Medical AI Inquiry: You was designed to assist in medical decision-making based on the provided user questions. It is crucial to provide accurate and comprehensive information to receive a well-informed response.  Labels: OBJECTIVE, METHODS, RESULTS. Meshes: ADAM Proteins, ADAMTS9 Protein, Cells, Cultured, Chondrocytes, Chondrosarcoma, Drug Synergism, Endopeptidases, Extracellular Signal-Regulated MAP Kinases, Humans, Interleukin-1, Metalloendopeptidases, Phosphorylation, Time Factors, Tumor Necrosis Factor-alpha.
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Is aDAMTS-9 synergistically induced by interleukin-1beta and tumor necrosis factor alpha in OUMS-27 chondrosarcoma cells and in human chondrocytes? Context: To compare induction of the aggrecanases (ADAMTS-1, ADAMTS-4, ADAMTS-5, ADAMTS-8, ADAMTS-9, and ADAMTS-15) by interleukin-1beta (IL-1beta) and tumor necrosis factor alpha (TNFalpha) in chondrocyte-like OUMS-27 cells and human chondrocytes, and to determine the mechanism of induction of the most responsive aggrecanase gene. OUMS-27 cells were stimulated for different periods of time and with various concentrations of IL-1beta and/or TNFalpha. Human chondrocytes obtained from osteoarthritic joints and human skin fibroblasts were also stimulated with IL-1beta and/or TNFalpha. Total RNA was extracted, reverse transcribed, and analyzed by quantitative real-time polymerase chain reaction and Northern blotting. ADAMTS-9 protein was examined by Western blotting, and the role of the MAPK signaling pathway for ADAMTS9 induction in IL-1beta-stimulated OUMS-27 cells was investigated. IL-1beta increased messenger RNA (mRNA) levels of ADAMTS4, ADAMTS5, and ADAMTS9 but not ADAMTS1 and ADAMTS8. The fold increase for ADAMTS9 mRNA was greater than that for mRNA of the other aggrecanase genes. The increase of ADAMTS9 mRNA by IL-1beta stimulation was greater in chondrocytes than in fibroblasts. The combination of IL-1beta and TNFalpha had a synergistic effect, resulting in a considerable elevation in the level of ADAMTS9 mRNA. ADAMTS-9 protein was also induced in IL-1beta-stimulated OUMS-27 cells. The MAPK inhibitors SB203580 and PD98059 decreased ADAMTS9 up-regulation in OUMS-27 cells.
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ADAMTS9 is an IL-1beta- and TNFalpha-inducible gene that appears to be more responsive to these proinflammatory cytokines than are other aggrecanase genes. Furthermore, these cytokines had a synergistic effect on ADAMTS9. Together with the known ability of ADAMTS-9 to proteolytically degrade aggrecan and its potential to cleave other cartilage molecules, the data suggest that ADAMTS-9 may have a pathologic role in arthritis. Final Decision: yes