Perturbation of a Cartilage Autocrine/Paracrine Basic Fibroblast Growth Factor Metabolic Regulatory Network by Osteoarthritic Synovial Tissue.
Studies have focused on control of expression and the relative importance of basic fibroblast growth factor (bFGF) in a purported autocrine/paracrine regulatory network functioning in the modulation of cartilage metabolic and structural homeostasis. Preformed and newly synthesized bFGF and concurrent antagonist activity could be identified by bioassay in cell/pericellular matrix extracts of normal bovine articular chondrocytes maintained in suspension culture. Specificity was determined using antibody neutralization. Prostanoids (PGE(1), PGE(2)) enhanced chondrocyte expression of the putative inhibitor. The antagonist, recognized in the presence of suboptimally triggered bFGF receptors, was active against both endogenously produced and recombinant bFGF. Chondrocyte expression of bFGF was significantly altered following exposure to conditioned medium obtained from explant cultures of osteoarthritic synovial tissue. Response pattern, that is, an upregulation or downregulation of growth factor expression, was dependent on medium concentration and the duration of chondrocyte exposure. Synovium-conditioned medium generated in the presence of PGE(1) appeared to attenuate suppressive responses seen with naive conditioned medium. Promotion of expression of bFGF inhibitory activity within the milieu of the diseased joint may negate potential detrimental pathophysiologic effects of this competence factor on cartilage, synovial tissue, and bone metabolism and repair.
Herman
Jerome H.
JH
Department of Internal Medicine, University of Cincinnati College of Medicine, Cincinnati, USA.
O'Connor
Michael P.
MP
Lieberman
Michael A.
MA