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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.

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