OBJECTIVE: To determine whether the basic fibroblast growth factor (bFGF) mediates signal transduction in articular cartilage in response to mechanical loading. METHODS: Articular cartilage from porcine metacarpophalangeal or knee joints was cyclically loaded (62.5-250N) for 2 minutes in the absence or presence of a bFGF receptor inhibitor, SB 402451 (250 nM). Activation of the extracellularly regulated kinase MAP kinase ERK was measured by Western blot analysis. Changes in protein synthesis were assessed by measuring the incorporation of (35)S-Met/Cys into proteins secreted by cartilage explants or by isolated chondrocytes. RESULTS: Rapid activation of the ERK MAP kinase occurred when articular cartilage was loaded. This was dependent upon release of the bFGF because it was restricted by the FGF receptor inhibitor. Loaded explants were shown to release bFGF. Loading or bFGF stimulation of explants induced synthesis and secretion of tissue inhibitor of metalloproteinases 1 (TIMP-1), which was inhibited by SB 402451. CONCLUSION: Cyclical loading of articular cartilage causes bFGF-dependent activation of ERK and synthesis of TIMP-1.
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Animals, Blotting, Western, Cartilage, Articular, Chondrocytes, Fibroblast Growth Factor 2, In Vitro Techniques, Mitogen-Activated Protein Kinases, Pyrimidines, Receptors, Fibroblast Growth Factor, Signal Transduction, Stifle, Stress, Mechanical, Swine, Tissue Inhibitor of Metalloproteinase-1, Weight-Bearing