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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: Adult, Aged, Aged, 80 and over, Animals, Arthritis, Arthritis, Experimental, Blotting, Western, Cells, Cultured, Female, Fluorescent Antibody Technique, HMGB1 Protein, Humans, Hypoxia, Inflammation, Interleukin-1, Joints, L-Lactate Dehydrogenase, Lactic Acid, Male, Mice, Middle Aged, Rats, Reverse Transcriptase Polymerase Chain Reaction, Severity of Illness Index, Synovial Fluid, Synovial Membrane, Tumor Necrosis Factor-alpha, Vascular Endothelial Growth Factor A.
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Is extracellular high mobility group box chromosomal protein 1 a coupling factor for hypoxia and inflammation in arthritis? Context: Tissue hypoxia is closely associated with arthritis pathogenesis, and extracellular high mobility group box chromosomal protein 1 (HMGB-1) released from injured cells also has a role in arthritis development. This study was thus undertaken to investigate the hypothesis that extracellular HMGB-1 may be a coupling factor between hypoxia and inflammation in arthritis. Concentrations of tumor necrosis factor alpha, interleukin-6, vascular endothelial growth factor, lactic acid, lactate dehydrogenase, and HMGB-1 were measured in synovial fluid (SF) samples from patients with inflammatory arthropathy (rheumatoid arthritis and pseudogout) and patients with noninflammatory arthropathy (osteoarthritis). The localization of tissue hypoxia and HMGB-1 was also examined in animal models of collagen-induced arthritis (CIA). In cell-based experiments, the effects of hypoxia on HMGB-1 release and its associated cellular events (i.e., protein distribution and cell viability) were studied. In SF samples from patients with HMGB-1-associated inflammatory arthropathy (i.e., samples with HMGB-1 levels >2 SD above the mean level in samples from patients with noninflammatory arthropathy), concentrations of HMGB-1 were significantly correlated with those of lactic acid, a marker of tissue hypoxia. In CIA models in which the pathologic phenotype could be attenuated by HMGB-1 neutralization, colocalization of HMGB-1 with tissue hypoxia in arthritis lesions was also observed. In cell-based experiments, hypoxia induced significantly increased levels of extracellular HMGB-1 by the cellular processes of secretion and/or apoptosis-associated release, which was much more prominent than the protein release in necrotic cell injury potentiated by oxidative stress.
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These findings indicate that tissue hypoxia and its resultant extracellular HMGB-1 might play an important role in the development of arthritis. Final Decision: yes