Possible involvement of IkappaB kinase 2 and MKK7 in osteoclastogenesis induced by receptor activator of nuclear factor kappaB ligand.
Recent studies have revealed the essential role of the receptor activator of nuclear factor kappaB (NF-kappaB) 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-kappaB and c-jun N-terminal kinase (JNK) activation in RANKL-induced osteoclast differentiation was investigated using an adenovirus vector carrying the dominant negative 1kappaB kinase 2 gene (AxIKK2DN) or dominant negative MKK7 gene (AxMKK7DN). IKK2DN and MKK7DN overexpression in RAW cells specifically suppressed the NF-kappaB activation and JNK activation in response to RANKL, respectively, without affecting other signaling pathways. Either inhibition of NF-kappaB or JNK pathways dose-dependently inhibited osteoclast formation induced by RANKL. These results suggest that both NF-kappaB and JNK activation are independently required for osteoclast differentiation.
Yamamoto
Aiichiro
A
Department of Orthopaedic Surgery, Faculty of Medicine, The University of Tokyo, Japan.
Miyazaki
Tsuyoshi
T
Kadono
Yuho
Y
Takayanagi
Hiroshi
H
Miura
Toshiki
T
Nishina
Hiroshi
H
Katada
Toshiaki
T
Wakabayashi
Kenji
K
Oda
Hiromi
H
Nakamura
Kozo
K
Tanaka
Sakae
S
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism*; D002454:Cell Differentiation / Q000235:genetics; D002478:Cells, Cultured; D004789:Enzyme Activation; D005799:Genes, Dominant; D051550:I-kappa B Kinase; D048031:JNK Mitogen-Activated Protein Kinases; D048688:MAP Kinase Kinase 7; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism*; D051379:Mice; D008815:Mice, Inbred Strains; D020929:Mitogen-Activated Protein Kinase Kinases / Q000235:genetics / Q000378:metabolism*; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D010010:Osteoclasts / Q000502:physiology*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; D013234:Stem Cells / Q000502:physiology
D002352:Carrier Proteins; D008562:Membrane Glycoproteins; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; C505687:Tnfrsf11a protein, mouse; C505689:Tnfsf11 protein, mouse; D017346:Protein Serine-Threonine Kinases; C496564:Chuk protein, mouse; D051550:I-kappa B Kinase; C496562:Ikbkb protein, mouse; C496566:Ikbke protein, mouse; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D048688:MAP Kinase Kinase 7; C482570:Map2k7 protein, mouse; D020929:Mitogen-Activated Protein Kinase Kinases