The association of notch2 and NF-kB accelerates RANKL-induced osteoclastogenesis

Hidefumi Fukushima, Akihiro Nakao, Fujio Okamoto, Masashi Shin, Hiroshi Kajiya, Seiji Sakano, Anna Bigas, Eijiro Jimi, Koji Okabe

Research output: Contribution to journalArticle

102 Citations (Scopus)

Abstract

Notch signaling plays a key role in various cell differentiation processes including bone homeostasis. However, the specific involvement of Notch in regulating osteoclastogenesis is still controversial. In the present study, we show that RANKL induces expression of Jaggedl and Notch2 in bone marrow macrophages during osteoclast differentiation. Suppression of Notch signaling by a selective γ-secretase inhibitor or Notch2 short hairpin RNA suppresses RANKL-induced osteoclastogenesis. In contrast, induction of Notch signaling by Jagged1 or by ectopic expression of intracellular Notch2 enhances NFATcl promoter activity and expression and promotes osteoclastogenesis. Finally, we found that Notch2 and p65 interact in the nuclei of RANKL-stimulated cells and that both proteins are recruited to the NFATc1 promoter, driving its expression. Taken together, our results show a new molecular cross talk between Notch and NF-κB pathways that is relevant in osteoclastogenesis.

Original languageEnglish
Pages (from-to)6402-6412
Number of pages11
JournalMolecular and cellular biology
Volume28
Issue number20
DOIs
Publication statusPublished - Oct 1 2008

Fingerprint

NF-kappa B
Osteogenesis
Amyloid Precursor Protein Secretases
Osteoclasts
Small Interfering RNA
Cell Differentiation
Homeostasis
Bone Marrow
Macrophages
Bone and Bones
Proteins

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cell Biology

Cite this

Fukushima, H., Nakao, A., Okamoto, F., Shin, M., Kajiya, H., Sakano, S., ... Okabe, K. (2008). The association of notch2 and NF-kB accelerates RANKL-induced osteoclastogenesis. Molecular and cellular biology, 28(20), 6402-6412. https://doi.org/10.1128/MCB.00299-08

The association of notch2 and NF-kB accelerates RANKL-induced osteoclastogenesis. / Fukushima, Hidefumi; Nakao, Akihiro; Okamoto, Fujio; Shin, Masashi; Kajiya, Hiroshi; Sakano, Seiji; Bigas, Anna; Jimi, Eijiro; Okabe, Koji.

In: Molecular and cellular biology, Vol. 28, No. 20, 01.10.2008, p. 6402-6412.

Research output: Contribution to journalArticle

Fukushima, H, Nakao, A, Okamoto, F, Shin, M, Kajiya, H, Sakano, S, Bigas, A, Jimi, E & Okabe, K 2008, 'The association of notch2 and NF-kB accelerates RANKL-induced osteoclastogenesis', Molecular and cellular biology, vol. 28, no. 20, pp. 6402-6412. https://doi.org/10.1128/MCB.00299-08
Fukushima H, Nakao A, Okamoto F, Shin M, Kajiya H, Sakano S et al. The association of notch2 and NF-kB accelerates RANKL-induced osteoclastogenesis. Molecular and cellular biology. 2008 Oct 1;28(20):6402-6412. https://doi.org/10.1128/MCB.00299-08
Fukushima, Hidefumi ; Nakao, Akihiro ; Okamoto, Fujio ; Shin, Masashi ; Kajiya, Hiroshi ; Sakano, Seiji ; Bigas, Anna ; Jimi, Eijiro ; Okabe, Koji. / The association of notch2 and NF-kB accelerates RANKL-induced osteoclastogenesis. In: Molecular and cellular biology. 2008 ; Vol. 28, No. 20. pp. 6402-6412.
@article{4760b5afecee4e3182d8e552d8e9f376,
title = "The association of notch2 and NF-kB accelerates RANKL-induced osteoclastogenesis",
abstract = "Notch signaling plays a key role in various cell differentiation processes including bone homeostasis. However, the specific involvement of Notch in regulating osteoclastogenesis is still controversial. In the present study, we show that RANKL induces expression of Jaggedl and Notch2 in bone marrow macrophages during osteoclast differentiation. Suppression of Notch signaling by a selective γ-secretase inhibitor or Notch2 short hairpin RNA suppresses RANKL-induced osteoclastogenesis. In contrast, induction of Notch signaling by Jagged1 or by ectopic expression of intracellular Notch2 enhances NFATcl promoter activity and expression and promotes osteoclastogenesis. Finally, we found that Notch2 and p65 interact in the nuclei of RANKL-stimulated cells and that both proteins are recruited to the NFATc1 promoter, driving its expression. Taken together, our results show a new molecular cross talk between Notch and NF-κB pathways that is relevant in osteoclastogenesis.",
author = "Hidefumi Fukushima and Akihiro Nakao and Fujio Okamoto and Masashi Shin and Hiroshi Kajiya and Seiji Sakano and Anna Bigas and Eijiro Jimi and Koji Okabe",
year = "2008",
month = "10",
day = "1",
doi = "10.1128/MCB.00299-08",
language = "English",
volume = "28",
pages = "6402--6412",
journal = "Molecular and Cellular Biology",
issn = "0270-7306",
publisher = "American Society for Microbiology",
number = "20",

}

TY - JOUR

T1 - The association of notch2 and NF-kB accelerates RANKL-induced osteoclastogenesis

AU - Fukushima, Hidefumi

AU - Nakao, Akihiro

AU - Okamoto, Fujio

AU - Shin, Masashi

AU - Kajiya, Hiroshi

AU - Sakano, Seiji

AU - Bigas, Anna

AU - Jimi, Eijiro

AU - Okabe, Koji

PY - 2008/10/1

Y1 - 2008/10/1

N2 - Notch signaling plays a key role in various cell differentiation processes including bone homeostasis. However, the specific involvement of Notch in regulating osteoclastogenesis is still controversial. In the present study, we show that RANKL induces expression of Jaggedl and Notch2 in bone marrow macrophages during osteoclast differentiation. Suppression of Notch signaling by a selective γ-secretase inhibitor or Notch2 short hairpin RNA suppresses RANKL-induced osteoclastogenesis. In contrast, induction of Notch signaling by Jagged1 or by ectopic expression of intracellular Notch2 enhances NFATcl promoter activity and expression and promotes osteoclastogenesis. Finally, we found that Notch2 and p65 interact in the nuclei of RANKL-stimulated cells and that both proteins are recruited to the NFATc1 promoter, driving its expression. Taken together, our results show a new molecular cross talk between Notch and NF-κB pathways that is relevant in osteoclastogenesis.

AB - Notch signaling plays a key role in various cell differentiation processes including bone homeostasis. However, the specific involvement of Notch in regulating osteoclastogenesis is still controversial. In the present study, we show that RANKL induces expression of Jaggedl and Notch2 in bone marrow macrophages during osteoclast differentiation. Suppression of Notch signaling by a selective γ-secretase inhibitor or Notch2 short hairpin RNA suppresses RANKL-induced osteoclastogenesis. In contrast, induction of Notch signaling by Jagged1 or by ectopic expression of intracellular Notch2 enhances NFATcl promoter activity and expression and promotes osteoclastogenesis. Finally, we found that Notch2 and p65 interact in the nuclei of RANKL-stimulated cells and that both proteins are recruited to the NFATc1 promoter, driving its expression. Taken together, our results show a new molecular cross talk between Notch and NF-κB pathways that is relevant in osteoclastogenesis.

UR - http://www.scopus.com/inward/record.url?scp=53549111642&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=53549111642&partnerID=8YFLogxK

U2 - 10.1128/MCB.00299-08

DO - 10.1128/MCB.00299-08

M3 - Article

VL - 28

SP - 6402

EP - 6412

JO - Molecular and Cellular Biology

JF - Molecular and Cellular Biology

SN - 0270-7306

IS - 20

ER -