|
|
Prepublished online as a Blood First Edition Paper on October 31, 2002; DOI 10.1182/blood-2002-06-1740.
Submitted June 13, 2002
Accepted October 21, 2002
Regulation of osteoclast development by Notch signaling directed to osteoclast precursors and through stromal cells
Takayuki Yamada*, Hidetoshi Yamazaki, Toshiyuki Yamane, Miya Yoshino, Hiromi Okuyama, Motokazu Tsuneto, Tomomi Kurino, Shin-Ichi Hayashi, and Seiji Sakano
Division of Immunology, Division of Immunology, Department of Molecular and Cellular Biology, School of Life Science, Faculty of Medicine, Tottori University, Tottori, Japan
Second Research Department, Central Technology Laboratory, Asahi Kasei Corp. Ltd., Shizuoka, Japan
* Corresponding author; email: yamad{at}grape.med.tottori-u.ac.jp.
Osteoclasts are derived from hematopoietic precursor cells belonging to the monocyte/macrophage lineage. Osteoclast development has been reported to be regulated by several molecules such as macrophage colony-stimulating factor (M-CSF), receptor activator of NF- B ligand (RANKL), and a decoy receptor of RANKL, osteoprotegerin (OPG). Recently it was demonstrated that the Notch signaling regulates myeloid differentiation and antagonizes cell fate determination, however, the effect of Notch signaling on the osteoclast lineage has not been reported yet. In this study, we examined the effect of signaling via Notch receptors on the differentiation into osteoclasts by using cells from the bone marrow, spleen, and peritoneal cavity, and a cloned macrophage-like cell line. The osteoclastogenesis was inhibited by an immobilized Notch ligand, Delta-1. The osteoclastogenesis of dish-adherent bone marrow cells, which were pre-cultured with M-CSF and expressed both Mac-1 and M-CSF receptor, c-Fms was efficiently inhibited. The immobilized Delta-1 also down-regulated the surface c-Fms expression, while the c-Fms gene expression was not changed. Genes for Notch receptors and Notch ligands are expressed in not only hematopoietic cells but also stromal cells which support osteoclast development. Constitutively active Notch1-transfected stromal cells showed increased expression of RANKL and OPG genes, and strong inhibition of M-CSF gene expression, resulting in reduction of their ability to support osteoclast development. Taken together, these findings indicate that Notch signaling affects both osteoclast precursors and stromal cells and thereby negatively regulates osteoclastogenesis.
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
This article has been cited by other articles:
|
|
|
|
 
P. Secchiero, E. Melloni, M. G. di Iasio, M. Tiribelli, E. Rimondi, F. Corallini, V. Gattei, and G. Zauli
Nutlin-3 up-regulates the expression of Notch1 in both myeloid and lymphoid leukemic cells, as part of a negative feedback antiapoptotic mechanism
Blood,
April 30, 2009;
113(18):
4300 - 4308.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
U. Styrkarsdottir, B. V. Halldorsson, S. Gretarsdottir, D. F. Gudbjartsson, G. B. Walters, T. Ingvarsson, T. Jonsdottir, J. Saemundsdottir, J. R. Center, T. V. Nguyen, et al.
Multiple Genetic Loci for Bone Mineral Density and Fractures
N. Engl. J. Med.,
May 29, 2008;
358(22):
2355 - 2365.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. Zhang, Y. Yang, P. A. Zweidler-McKay, and D. P.M. Hughes
Critical Role of Notch Signaling in Osteosarcoma Invasion and Metastasis
Clin. Cancer Res.,
May 15, 2008;
14(10):
2962 - 2969.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Bai, R. Kopan, W. Zou, M. J. Hilton, C.-t. Ong, F. Long, F. P. Ross, and S. L. Teitelbaum
NOTCH1 Regulates Osteoclastogenesis Directly in Osteoclast Precursors and Indirectly via Osteoblast Lineage Cells
J. Biol. Chem.,
March 7, 2008;
283(10):
6509 - 6518.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
V. Bolos, J. Grego-Bessa, and J. L. de la Pompa
Notch Signaling in Development and Cancer
Endocr. Rev.,
May 1, 2007;
28(3):
339 - 363.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. G. Leong and A. Karsan
Recent insights into the role of Notch signaling in tumorigenesis
Blood,
March 15, 2006;
107(6):
2223 - 2233.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. Takeuchi, Y. Adachi, and Y. Ohtsuki
Skeletrophin, a Novel Ubiquitin Ligase to the Intracellular Region of Jagged-2, Is Aberrantly Expressed in Multiple Myeloma
Am. J. Pathol.,
June 1, 2005;
166(6):
1817 - 1826.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Nobta, T. Tsukazaki, Y. Shibata, C. Xin, T. Moriishi, S. Sakano, H. Shindo, and A. Yamaguchi
Critical Regulation of Bone Morphogenetic Protein-induced Osteoblastic Differentiation by Delta1/Jagged1-activated Notch1 Signaling
J. Biol. Chem.,
April 22, 2005;
280(16):
15842 - 15848.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S.-I. Hayashi, M. Tsuneto, T. Yamada, M. Nose, M. Yoshino, L. D. Shultz, and H. Yamazaki
Lipopolysaccharide-Induced Osteoclastogenesis in Src Homology 2-Domain Phosphatase-1-Deficient Viable Motheaten Mice
Endocrinology,
June 1, 2004;
145(6):
2721 - 2729.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S.-I. Hayashi, T. Yamada, M. Tsuneto, T. Yamane, M. Takahashi, L. D. Shultz, and H. Yamazaki
Distinct Osteoclast Precursors in the Bone Marrow and Extramedullary Organs Characterized by Responsiveness to Toll-Like Receptor Ligands and TNF-{alpha}
J. Immunol.,
November 15, 2003;
171(10):
5130 - 5139.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
