%0 Journal Article
%T Fibroblast growth factor 2: good or bad guy in the joint?
%A Tonia L Vincent
%J Arthritis Research & Therapy
%D 2011
%I BioMed Central
%R 10.1186/ar3447
%X Fibroblast growth factor (FGF)2 is a ubiquitously expressed pleiotropic growth factor with many recognised cellular targets and tissue effects. Its role in articular chondrocytes and mesenchymal cells has been extensively studied, but published data are plagued by apparent contradiction and inconsistency. The paper by Yan and colleagues reported in the previous issue of Arthritis Research & Therapy proposes a novel and elegant explanation for these seemingly disparate and conflicting findings [1]. FGFs signal through one of four FGF receptors (FGFRs), and the authors show that the catabolic effects of FGF2 (induction of proteases such as matrix metalloproteinase 13 (MMP13) and ADAMTS5 (a disintegrin and metalloproteinase with thrombospondin motifs 5)), as well as suppression of matrix synthesis, are specifically mediated through FGFR1 ligation. They propose that FGF2 signalling via FGFR3, the other major cell surface receptor on chondrocytes, leads to a dominant anabolic drive. This is supported by the finding that FGF18, which is unusual because it is less promiscuous than FGF2 and selectively activates only FGFR3 [2], is able to stimulate proteoglycan synthesis. Other reports have confirmed the anabolic nature of FGF18 and an ongoing clinical trial of intraarticular injection of recombinant FGF18 in osteoarthritis is currently being conducted by Merck Serono (reviewed in [3]).Our own studies have demonstrated that FGF2 is stored within the pericellular matrix of chondrocytes attached to the heparan sulphate chains of perlecan [4]. This pool of growth factor is liberated upon injury or mechanical compression of the matrix [5]. We demonstrated that, at least in young mice, the overall effect of FGF2 in the joint is benign. Indeed, mice lacking FGF2 (FGF2 null mice) developed accelerated osteoarthritis (with age and following surgical joint destabilisation), and this could be reversed by delivery of subcutaneous recombinant FGF2 [6]. When gene expression analysis was
%U http://arthritis-research.com/content/13/5/127