Basic fibroblast growth factor mediates transduction of mechanical signals when articular cartilage is loaded
Article first published online: 5 FEB 2004
Copyright © 2004 by the American College of Rheumatology
Arthritis & Rheumatism
Volume 50, Issue 2, pages 526–533, February 2004
How to Cite
Vincent, T. L., Hermansson, M. A., Hansen, U. N., Amis, A. A. and Saklatvala, J. (2004), Basic fibroblast growth factor mediates transduction of mechanical signals when articular cartilage is loaded. Arthritis & Rheumatism, 50: 526–533. doi: 10.1002/art.20047
- Issue published online: 5 FEB 2004
- Article first published online: 5 FEB 2004
- Manuscript Accepted: 13 NOV 2003
- Manuscript Received: 28 MAY 2003
- Wellcome Trust
- Arthritis Research Campaign
- Medical Research Council of the UK
To determine whether the basic fibroblast growth factor (bFGF) mediates signal transduction in articular cartilage in response to mechanical loading.
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 35S-Met/Cys into proteins secreted by cartilage explants or by isolated chondrocytes.
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.
Cyclical loading of articular cartilage causes bFGF-dependent activation of ERK and synthesis of TIMP-1.