Possible involvement of IκB kinase 2 and MKK7 in osteoclastogenesis induced by receptor activator of nuclear factor κB ligand

Abstract

Recent studies have revealed the essential role of the receptor activator of nuclear factor κB (NF-κB) ligand (RANKL) in osteoclast differentiation and activation. Adenovirus vector could efficiently transduce genes into RAW264.7 cells, which differentiate into osteoclast-like multinucleated cells in the presence of RANKL. The role of NF-κB and c-jun N-terminal kinase (JNK) activation in RANKL-induced osteoclast differentiation was investigated using an adenovirus vector carrying the dominant negative IκB kinase 2 gene (AxIKK2DN) or dominant negative MKK7 gene (AxMKK7DN). IKK2DN and MKK7DN overexpression in RAW cells specifically suppressed the NF-κB activation and JNK activation in response to RANKL, respectively, without affecting other signaling pathways. Either inhibition of NF-κB or JNK pathways dose-dependently inhibited osteoclast formation induced by RANKL. These results suggest that both NF-κB and JNK activation are independently required for osteoclast differentiation.