Fibroblast growth factor signalling in osteoarthritis and cartilage repair

Abstract

Regulated fibroblast growth factor (FGF) signalling is a prerequisite for the correct development and homeostasis of articular cartilage, as evidenced by the fact that aberrant FGF signalling contributes to the maldevelopment of joints and to the onset and progression of osteoarthritis. Of the four FGF receptors (FGFRs 1-4), FGFR1 and FGFR3 are strongly implicated in osteoarthritis, and FGFR1 antagonists, as well as agonists of FGFR3, have shown therapeutic efficacy in mouse models of spontaneous and surgically induced osteoarthritis. FGF18, a high affinity ligand for FGFR3, is the only FGF-based drug currently in clinical trials for osteoarthritis. This Review covers the latest advances in our understanding of the molecular mechanisms that regulate FGF signalling during normal joint development and in the pathogenesis of osteoarthritis. Strategies for FGF signalling-based treatment of osteoarthritis and for cartilage repair in animal models and clinical trials are also introduced. An improved understanding of FGF signalling from a structural biology perspective, and of its roles in skeletal development and diseases, could unlock new avenues for discovery of modulators of FGF signalling that can slow or stop the progression of osteoarthritis.