The Mechanism of Bone Resorption Induced by Epiregulin, a Member of EGF Family

Abstract

We investigated the effect of epiregulin (EPR) and EGF on the bone resorption using mice bones and cells. Both EPR and EGF enhanced bone resorption in ⁴⁵Ca-prelabeled parietal bone without affecting osteoclast differentiation. These growth factors also enhanced the pit formation by femur-derived osteoclastrich fraction without increasing the number of the osteoclasts in a NS-398 (a COX-2 inhibitor)- sensitive manner. Furthermore, mature osteoclasts, differentiated from RANKL-stimulated RAW264.7 cells, induced pit formation with a longer time of EPR in a gefitinib (an EGFR tyrosinekinase inhibitor)-sensitive manner. These findings suggest that both EPR and EGF acted on osteoblasts to enhance bone resorption indirectly. In addition, EPR is suggested to have a direct stimulating pathway through the activation of EGFR on mature osteoclasts leading to bone resorption.