system
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: METHODS, OBJECTIVE, BACKGROUND, METHODS, RESULTS. Meshes: ADAM Proteins, Aggrecans, Animals, Cattle, Chondroitin Sulfate Proteoglycans, Collagen, Dose-Response Relationship, Drug, Extracellular Matrix, Extracellular Matrix Proteins, Gene Expression, Humans, Intervertebral Disc, Lectins, C-Type, Matrix Metalloproteinases, Proteoglycans, Recombinant Proteins, Tissue Culture Techniques, Tissue Inhibitor of Metalloproteinases, Tumor Necrosis Factor-alpha.
user
Does tumor necrosis factor-alpha modulate matrix production and catabolism in nucleus pulposus tissue? Context: This study examines changes in the production of extracellular matrix molecules as well as the induction of tissue degradation in in vitro formed nucleus pulposus (NP) tissues following incubation with tumor necrosis factor (TNF)alpha. To characterize the response of NP cells to TNF-alpha, a proinflammatory cytokine present in herniated NP tissues. TNF-alpha is a proinflammatory cytokine expressed by NP cells of degenerate intervertebral discs. It is implicated in the pain associated with disc herniation, although its role in intervertebral disc degeneration remains poorly understood. In vitro formed NP tissues were treated with TNF-alpha (up to 50 ng/mL) over 48 hours. Tissues were assessed for histologic appearance, proteoglycan and collagen contents, as well as proteoglycan and collagen synthesis. Reverse transcriptase polymerase chain reaction was used to determine the effect of TNF-alpha on NP cell gene expression. Proteoglycan degradation was assessed by immunoblot analysis. At doses of 1-5 ng/mL, TNF-alpha induced multiple cellular responses, including: decreased expression of both aggrecan and type II collagen genes; decreases in the accumulation and overall synthesis of aggrecan and collagen; increased expression of MMP-1, MMP-3, MMP-13, ADAM-TS4, and ADAM-TS5; and induction of ADAM-TS dependent proteoglycan degradation. Within 48 hours, these cellular responses resulted in NP tissue with only 25% of its original proteoglycan content.
assistant
Because low levels of TNF-alpha, comparable to those present physiologically, induced NP tissue degradation, this suggests that TNF-alpha may contribute to the degenerative changes that occur in disc disease. Final Decision: yes