Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents

This Article Full Text Full Text (PDF, 599K) PPT slides of all figures Alert me when this article is cited Citation Map Services Email this article Similar articles in this journal Similar articles in PubMed Alert me to new content in the JEM Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Arai, F. Articles by Suda, T. Search for Related Content PubMed PubMed Citation Articles by Arai, F. Articles by Suda, T. Social Bookmarking                            What's this?

Original Article

Commitment and Differentiation of Osteoclast Precursor Cells by the Sequential Expression of C-Fms and Receptor Activator of Nuclear Factor b (Rank) Receptors

^a Department of Cell Differentiation, Institute of Molecular Embryology and Genetics, Kumamoto University School of Medicine, Kumamoto 860-0811, Japan
^b Department of Periodontology, Meikai University School of Dentistry, Sakado 350-0248, Japan
^c Basic Research Laboratories, Toray Industries, Incorporated, Kamakura 248-0036, Japan
^d Department of Molecular Biology, Immunex Corporation, Seattle, Washington 98101-2936
Dept. of Cell Differentiation, Institute of Molecular Embryology and Genetics (IMEG), Kumamoto University School of Medicine, 2-2-1 Honjo, Kumamoto 860-0811, Japan.81-96-373-533281-96-373-5328

sudato{at}gpo.kumamoto-u.ac.jp

Osteoclasts are terminally differentiated cells derived from hematopoietic stem cells. However, how their precursor cells diverge from macrophagic lineages is not known. We have identified early and late stages of osteoclastogenesis, in which precursor cells sequentially express c-Fms followed by receptor activator of nuclear factor B (RANK), and have demonstrated that RANK expression in early-stage of precursor cells (c-Fms⁺RANK^–) was stimulated by macrophage colony-stimulating factor (M-CSF). Although M-CSF and RANKL (ligand) induced commitment of late-stage precursor cells (c-Fms⁺RANK⁺) into osteoclasts, even late-stage precursors have the potential to differentiate into macrophages without RANKL. Pretreatment of precursors with M-CSF and delayed addition of RANKL showed that timing of RANK expression and subsequent binding of RANKL are critical for osteoclastogenesis. Thus, the RANK–RANKL system determines the osteoclast differentiation of bipotential precursors in the default pathway of macrophagic differentiation.

Key Words: osteoclastogenesis • commitment • macrophage • RANK ligand • M-CSF

Abbreviations used in this paper: BM, bone marrow; Dex, dexamethasone; Epo, erythropoietin; L, ligand; MNCs, multinucleated cells; NF, nuclear factor; OPG, osteoprotegerin; RANK, receptor activator of nuclear factor B; RT, reverse transcriptase; s, soluble; SCF, stem cell factor; TRAFs, TNFR-associated factors; TRAP, tartrate-resistant acid phosphatase.

© 1999 The Rockefeller University Press

CiteULike    Complore    Connotea    Del.icio.us    Digg    Facebook    Reddit    Technorati    Twitter    What's this?

This article has been cited by other articles:

• Ji, J.-D., Park-Min, K.-H., Shen, Z., Fajardo, R. J., Goldring, S. R., McHugh, K. P., Ivashkiv, L. B. (2009). Inhibition of RANK Expression and Osteoclastogenesis by TLRs and IFN-{gamma} in Human Osteoclast Precursors. J. Immunol. 183: 7223-7233 [Abstract] [Full Text]  
• Lee, Y., Ha, J., Kim, H. J., Kim, Y.-S., Chang, E.-J., Song, W.-J., Kim, H.-H. (2009). Negative Feedback Inhibition of NFATc1 by DYRK1A Regulates Bone Homeostasis. J. Biol. Chem. 284: 33343-33351 [Abstract] [Full Text]  

Home | Help | Feedback | Subscriptions | Archive | Search

TABLE OF CONTENTS