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

Aiichiro Yamamoto; Tsuyoshi Miyazaki; Yuho Kadono; Hiroshi Takayanagi; Toshiki Miura; Hiroshi Nishina; Toshiaki Katada; Kenji Wakabayashi; Hiromi Oda; Kozo Nakamura; Sakae Tanaka

doi:10.1359/jbmr.2002.17.4.612

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

J Bone Miner Res. 2002 Apr;17(4):612-21. doi: 10.1359/jbmr.2002.17.4.612.

Authors

Aiichiro Yamamoto¹, Tsuyoshi Miyazaki, Yuho Kadono, Hiroshi Takayanagi, Toshiki Miura, Hiroshi Nishina, Toshiaki Katada, Kenji Wakabayashi, Hiromi Oda, Kozo Nakamura, Sakae Tanaka

Affiliation

¹ Department of Orthopaedic Surgery, Faculty of Medicine, The University of Tokyo, Japan.

PMID: 11918218
DOI: 10.1359/jbmr.2002.17.4.612

Abstract

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adenoviridae / genetics
Animals
Carrier Proteins / metabolism*
Cell Differentiation / genetics
Cells, Cultured
Enzyme Activation
Genes, Dominant
I-kappa B Kinase
JNK Mitogen-Activated Protein Kinases
MAP Kinase Kinase 7
Male
Membrane Glycoproteins / metabolism*
Mice
Mice, Inbred Strains
Mitogen-Activated Protein Kinase Kinases / genetics
Mitogen-Activated Protein Kinase Kinases / metabolism*
Mitogen-Activated Protein Kinases / metabolism
Osteoclasts / physiology*
Protein Serine-Threonine Kinases / genetics
Protein Serine-Threonine Kinases / metabolism*
RANK Ligand
Receptor Activator of Nuclear Factor-kappa B
Stem Cells / physiology

Substances

Carrier Proteins
Membrane Glycoproteins
RANK Ligand
Receptor Activator of Nuclear Factor-kappa B
Tnfrsf11a protein, mouse
Tnfsf11 protein, mouse
Protein Serine-Threonine Kinases
Chuk protein, mouse
I-kappa B Kinase
Ikbkb protein, mouse
Ikbke protein, mouse
JNK Mitogen-Activated Protein Kinases
Mitogen-Activated Protein Kinases
MAP Kinase Kinase 7
Map2k7 protein, mouse
Mitogen-Activated Protein Kinase Kinases