| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
Endocrinology, Vol 136, 2367-2376, Copyright © 1995 by Endocrine Society
ARTICLES |
DL Lacey, JM Erdmann, SL Teitelbaum, HL Tan, J Ohara and A Shioi
Department of Pathology, Jewish Hospital, Washington University, St. Louis, Missouri 63110, USA.
Interleukin 4 (IL-4) is an immune cytokine that inhibits bone resorption in mice and suppresses osteoclastic cell formation in vitro through an undefined mechanism. In this report, we have established the cellular identity of the IL-4 target cell using a variety of bone marrow/stromal cell coculture methods. Initially, we found that the majority of IL-4's inhibition of osteoclastic cell formation was due to its effect on bone marrow cells, not stromal cells. Consequently, bone marrow macrophages were used as osteoclastic cell progenitors after they had been transiently exposed to IL-4 (48 h), before the addition of stromal cells, 1,25-dihydroxyvitamin D3, and dexamethasone. In this circumstance, IL-4 impaired subsequent osteoclastic cell formation, suggesting that the macrophage may be potentially targeted by many factors known to influence osteoclast formation. Consequently, we discovered that interferon-gamma (IFN gamma), prostaglandin E (PGE), and cell-permeant cAMP analogs also impacted osteoclastic cell formation when used to selectively treat bone marrow macrophages. IFN gamma suppressed osteoclastic cell formation, whereas PGE and cAMP analog treatment led to the formation of significantly enlarged osteoclastic cells. Importantly, PGE antagonized the inhibitory effects of both IL-4 and IFN gamma on the osteoclastic cell-forming potential of bone marrow macrophages. Collectively, these findings establish bone marrow macrophages as osteoclastic cell precursors with the degree of their commitment to the osteoclast pathway sensitive to the effects of soluble mediators, including IL-4, IFN gamma, and PGE.
This article has been cited by other articles:
 |
|
 |
|
  J. L. Moreno, I. Mikhailenko, M. M. Tondravi, and A. D. Keegan IL-4 promotes the formation of multinucleated giant cells from macrophage precursors by a STAT6-dependent, homotypic mechanism: contribution of E-cadherin J. Leukoc. Biol., December 1, 2007; 82(6): 1542 - 1553. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Mochizuki, M. Takami, T. Kawawa, R. Suzumoto, T. Sasaki, A. Shiba, H. Tsukasaki, B. Zhao, R. Yasuhara, T. Suzawa, et al. Identification and Characterization of the Precursors Committed to Osteoclasts Induced by TNF-Related Activation-Induced Cytokine/Receptor Activator of NF-{kappa}B Ligand J. Immunol., October 1, 2006; 177(7): 4360 - 4368. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 I. Take, Y. Kobayashi, Y. Yamamoto, H. Tsuboi, T. Ochi, S. Uematsu, N. Okafuji, S. Kurihara, N. Udagawa, and N. Takahashi Prostaglandin E2 Strongly Inhibits Human Osteoclast Formation Endocrinology, December 1, 2005; 146(12): 5204 - 5214. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. L. Moreno, M. Kaczmarek, A. D. Keegan, and M. Tondravi IL-4 suppresses osteoclast development and mature osteoclast function by a STAT6-dependent mechanism: irreversible inhibition of the differentiation program activated by RANKL Blood, August 1, 2003; 102(3): 1078 - 1086. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. W. Fox, S. J. Haque, A. C. Lovibond, and T. J. Chambers The Possible Role of TGF-{beta}-Induced Suppressors of Cytokine Signaling Expression in Osteoclast/Macrophage Lineage Commitment In Vitro J. Immunol., April 1, 2003; 170(7): 3679 - 3687. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Cuzzocrea, E. Mazzon, L. Dugo, T. Genovese, R. Di Paola, Z. Ruggeri, E. Vegeto, A. P. Caputi, F. A. J. Van de Loo, D. Puzzolo, et al. Inducible Nitric Oxide Synthase Mediates Bone Loss in Ovariectomized Mice Endocrinology, March 1, 2003; 144(3): 1098 - 1107. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Bouchard, R. de Medicis, A. Lussier, P. H. Naccache, and P. E. Poubelle Inflammatory Microcrystals Alter the Functional Phenotype of Human Osteoblast-Like Cells In Vitro: Synergism with IL-1 to Overexpress Cyclooxygenase-2 J. Immunol., May 15, 2002; 168(10): 5310 - 5317. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Tintut, F. Parhami, A. Tsingotjidou, S. Tetradis, M. Territo, and L. L. Demer 8-Isoprostaglandin E2 Enhances Receptor-activated NFkappa B Ligand (RANKL)-dependent Osteoclastic Potential of Marrow Hematopoietic Precursors via the cAMP Pathway J. Biol. Chem., April 12, 2002; 277(16): 14221 - 14226. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Wei, M. W.-H. Wang, S. L. Teitelbaum, and F. P. Ross Interleukin-4 Reversibly Inhibits Osteoclastogenesis via Inhibition of NF-kappa B and Mitogen-activated Protein Kinase Signaling J. Biol. Chem., February 15, 2002; 277(8): 6622 - 6630. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. J. Horwood, J. Elliott, T. J. Martin, and M. T. Gillespie IL-12 Alone and in Synergy with IL-18 Inhibits Osteoclast Formation In Vitro J. Immunol., April 15, 2001; 166(8): 4915 - 4921. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. C. Bendixen, N. K. Shevde, K. M. Dienger, T. M. Willson, C. D. Funk, and J. W. Pike IL-4 inhibits osteoclast formation through a direct action on osteoclast precursors via peroxisome proliferator-activated receptor gamma 1 PNAS, February 15, 2001; (2001) 41493198. [Abstract] [Full Text]
|
|
|
|
|
|
S. W. Fox, K. Fuller, K. E. Bayley, J. M. Lean, and T. J. Chambers TGF-{beta}1 and IFN-{gamma} Direct Macrophage Activation by TNF-{alpha} to Osteoclastic or Cytocidal Phenotype J. Immunol., November 1, 2000; 165(9): 4957 - 4963. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. G. Emery, P. McDonnell, M. B. Burke, K. C. Deen, S. Lyn, C. Silverman, E. Dul, E. R. Appelbaum, C. Eichman, R. DiPrinzio, et al. Osteoprotegerin Is a Receptor for the Cytotoxic Ligand TRAIL J. Biol. Chem., June 5, 1998; 273(23): 14363 - 14367. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Bucay, I. Sarosi, C. R. Dunstan, S. Morony, J. Tarpley, C. Capparelli, S. Scully, H. L. Tan, W. Xu, D. L. Lacey, et al. osteoprotegerin-deficient mice develop early onset osteoporosis and arterial calcification Genes & Dev., May 1, 1998; 12(9): 1260 - 1268. [Abstract] [Full Text]
|
|
|
|
|
|
T. Wakikawa, A. Shioi, M. Hino, M. Inaba, Y. Nishizawa, N. Tatsumi, H. Morii, and S. Otani Thrombopoietin Inhibits in Vitro Osteoclastogenesis from Murine Bone Marrow Cells Endocrinology, October 1, 1997; 138(10): 4160 - 4166. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Udagawa, N. J. Horwood, J. Elliott, A. Mackay, J. Owens, H. Okamura, M. Kurimoto, T. J. Chambers, T. J. Martin, and M. T. Gillespie Interleukin-18 (Interferon-gamma -inducing Factor) Is Produced by Osteoblasts and Acts Via Granulocyte/Macrophage Colony-stimulating Factor and Not Via Interferon-gamma to Inhibit Osteoclast Formation J. Exp. Med., March 17, 1997; 185(6): 1005 - 1012. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. C. Bendixen, N. K. Shevde, K. M. Dienger, T. M. Willson, C. D. Funk, and J. W. Pike IL-4 inhibits osteoclast formation through a direct action on osteoclast precursors via peroxisome proliferator-activated receptor gamma 1 PNAS, February 27, 2001; 98(5): 2443 - 2448. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Endocrinology | Endocrine Reviews | J. Clin. End. & Metab. |
| Molecular Endocrinology | Recent Prog. Horm. Res. | All Endocrine Journals |
