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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: Animals, Biological Products, Blotting, Northern, Cattle, Cells, Cultured, Chondrocytes, Collagen, Dose-Response Relationship, Drug, Enzyme-Linked Immunosorbent Assay, Humans, Hydroxyproline, Interleukin-1, Matrix Metalloproteinases, Methylene Blue, Proteoglycans, Tissue Inhibitor of Metalloproteinase-1, Umbelliferones.
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Does esculetin inhibit cartilage resorption induced by interleukin 1alpha in combination with oncostatin M? Context: To determine if a new inhibitor, esculetin (EST), can block resorption of cartilage. Interleukin 1alpha (IL1alpha, 0.04-5 ng/ml) and oncostatin M (OSM, 0.4-50 ng/ml) were used to stimulate the release of proteoglycan and collagen from bovine nasal cartilage and human articular cartilage in explant culture. Proteoglycan and collagen loss were assessed by dimethylmethylene blue and hydroxyproline assays, respectively. Collagenase levels were measured by assay of bioactivity and by enzyme linked immunosorbent assay (ELISA). The effects of EST on the expression of matrix metalloproteinases (MMPs) and tissue inhibitor of metalloproteinase-1 (TIMP-1) in the transformed human chondrocyte cell line T/C28a4 were assessed by northern blot analysis. TIMP-1 protein levels were assayed by ELISA. The effect of EST on the MMP-1 promoter was assessed using a promoter-luciferase construct in transient transfection studies. EST inhibited proteoglycan and collagen resorption in a dose dependent manner with significant decreases seen at 66 microM and 100 microM EST, respectively. Collagenolytic activity was significantly decreased in bovine nasal cartilage cultures. In human articular cartilage, EST also inhibited IL1alpha + OSM stimulated resorption and decreased MMP-1 levels. TIMP-1 levels were not altered compared with controls. In T/C28a4 chondrocytes the IL1alpha + OSM induced expression of MMP-1, MMP-3, and MMP-13 mRNA was reduced to control levels by 250 microM EST. TIMP-1 mRNA levels were unaffected by EST treatment. All cytokine stimulation of an MMP-1 luciferase-promoter construct was lost in the presence of the inhibitor.
assistant
EST inhibits degradation of bovine nasal cartilage and human articular cartilage stimulated to resorb with IL1alpha + OSM. Final Decision: yes