FGF18

Fibroblast growth factor 18 (FGF-18) is a protein that is encoded by the FGF18 gene in humans. The protein was first discovered in 1998, when two newly-identified murine genes Fgf17 and Fgf18 were described and confirmed as being closely related by sequence homology to Fgf8. The three proteins were eventually grouped into the FGF8 subfamily, which contains several of the endocrine FGF superfamily members FGF8, FGF17, and FGF18. Subsequent studies identified FGF18's role in promoting chondrogenesis, and an apparent specific activity for the generation of the hyaline cartilage in articular joints.

The protein encoded by this gene is a member of the fibroblast growth factor (FGF) family. FGF family members possess broad mitogenic and cell survival activities, and are involved in a variety of biological processes, including embryonic development, cell growth, morphogenesis, and tissue repair. It has been shown in vitro that this protein is able to induce neurite outgrowth in PC12 cells.

Function
FGF18 signals through fibroblast growth factor receptor (FGFR) family, preferentially binding FGFR 3c (followed by 4△, 2c, 1c, and finally 3b), signaling via FGFR3 promotes generation of cartilage (chondrogenesis). FGF18 and has been shown to cause thickening of cartilage in a murine model of osteoarthritis, and the recombinant version of it (sprifermin) is in a clinical trial as a potential treatment for osteoarthritis (OA). Recent findings from a placebo-controlled randomized clinical study demonstrate the potential of FGF18 to reduce the rate of progression to joint replacement surgery and delay progression of OA-related pain (WOMAC). Another study suggested the ability of FGF18 to inhibit intravertebral disc degeneration in a rabbit model of the disease.

Studies of the similar proteins in mouse and chick suggested that this protein is a pleiotropic growth factor that stimulates proliferation in a number of tissues, most notably the liver and small intestine. Knockout studies of the similar gene in mice implied the role of this protein in regulating proliferation and differentiation of midline cerebellar structures.

FGF18 appears to be a pleiotropic factor, expressed in a broad range of tissues and organs; the highest level of FGF18 expression were confirmed in the right ventricle interventricular septum of the heart. The role of FGF18 in the heart appears to be associated with protection from stress-induced pathological cardiac hypertrophy via the induction of survival or regenerative signals. Similarly, studies confirmed that overexpression of FGF18 in the liver was able to attenuate liver fibrosis following chemically-induced injury.

Studies of FGF18 in relation to oncology have shown both decreased levels and increased levels of FGF18 in a number of cancer types and stages, however, FGF18 does not appear to be causative or prognostic and long-term clinical studies of the FGF18 analog, sprifermin, have demonstrated an excellent safety profile with no reported oncogenic effects.