The epidermal growth factor receptor plays an anabolic role in bone

The epidermal growth factor receptor (EGFR) is a tyrosine kinase receptor present at the cell surface. EGFR binds EGF-like ligands including EGF, amphiregulin, transforming growth factor α (TGF-α), heparin binding EGF (HBEGF), betacellulin (BTC) and epiregulin. Upon activation by its ligands, EGFR is activated by dimerization with phosphorylation on tyrosine residues of its intracellular tail. Then a variety of signaling pathways are recruited by the phosphorylated EGFR to influence cell behavior.

In vitro studies have shown that EGFR signaling plays an important role in bone metabolism by affecting both bone formation and resorption. In vivo, EGFR deficiency leads to early lethality with severe developmental abnormalities associated with trabecular bone formation impairment. Mice humanized for EGFR are growth retarded without bone remodeling defects. Interestingly, these two mouse models present a dramatic bone abnormality with an enlarged hypertrophic chondrocyte zone in the growth plate, suggesting that EGFR may play a role in chondrocyte terminal differentiation.

Available data demonstrate that EGFR plays primarily an anabolic role in bone metabolism. The EGF pathway may therefore represent an interesting bone anabolic drug target.

1. Schneider MR et al. Trends Endocrinol Metab.. 2009;20:517-524.