| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
* Department of Microbiology and Immunology, School of Medicine and Dentistry, University of Rochester, Rochester, NY 14620;
Department of Microbiology and Immunology, Faculty of Medicine and Dentistry, University of Western Ontario, London, Ontario, Canada; and
Institute of Molecular Biotechnology of the Austrian Academy of Sciences, Vienna, Austria
Dendritic cells (DC) are innate immune effectors and are critically involved in regulating T cell immunity. Osteoclasts (OC) are bone-resorbing cells derived from the monocyte/macrophage lineage in response to receptor activator of NF-
B ligand (RANKL). DC and T cells form aggregates in the inflammatory infiltrates at active disease sites in human and in experimental rheumatoid arthritis and periodontitis. We investigated whether DC interactions with T cells in the bone environment can support the development of functional OC. In the present study, we demonstrate that upon proper activation by microbial or protein Ags (namely Actinobacillus actinomycetemcomitans, bovine insulin, and outer membrane protein-1) and during immune interactions with CD4+ T cells in vitro, murine BM-derived and splenic CD11c+ DC (CD11b–F4/80–Ly-6C–CD31–) develop into TRAP+CT-R+cathepsin-k+ functional OC in a RANKL/RANK-dependent manner. Rescue and blocking experiments using CD11c+ DC derived from Csf-1–/–op/op mice show that M-CSF is required "before" developing such osteoclastogenic potential upstream of RANKL/RANK signaling, suggesting that immature CD11c+ DC can indeed act like OC precursors. In addition, these CD11c+ DC-derived OC are capable of inducing bone loss after adoptive transfer in vivo. These data suggest a direct contribution of DC during immune interactions with CD4+ T cells to inflammation-induced osteoclastogenesis. Therefore, our findings not only provide further evidence for DC plasticity, but also extend the current paradigm of osteoimmunology.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 This work was supported by grants from the Ministry of Health of Ontario and the Canadian Institute of Health Research Grant MOP-37960, University of Rochester, and National Institutes of Health Grants DE14473 and DE15786 (to Y.-T.A.T.).
2 Address correspondence and reprint requests to Dr. Yen-Tung Andy Teng, Department of Microbiology and Immunology, School of Medicine and Dentistry, University of Rochester, Rochester, NY 14620. E-mail address: andy_teng{at}urmc.rochester.edu
3 Abbreviations used in this paper: RA, rheumatoid arthritis; Aa, Actinobacillus actinomycetemcomitans; AMCA, 7-amino-4-methylcoumarin-3-acetic acid; BI, bovine insulin; BM, bone marrow; CT-R, calcitonin receptor; DC, dendritic cell; DDOC, DC-derived osteoclast; HA, hydroxyapatite; IF, immunofluorescent; m, mouse; MHC-II, MHC class II; Mo/MQ, monocyte/macrophage; RANK, receptor activator of NF-B; RANKL, receptor activator of NF-B ligand; OB, osteoblast; OMP-1, outer membrane protein-1; OC, osteoclast; OPG, osteoprotegerin; PD, periodontal disease (or periodontitis); s, soluble; SIDIA, scanning IF digital images analysis; TRAP, tartrate resistance acid phosphatase; WT, wild type.
This article has been cited by other articles:
|
|
 |
|
  E.-J. Chang, J. Ha, H. Huang, H. J. Kim, J. H. Woo, Y. Lee, Z. H. Lee, J. H. Kim, and H.-H. Kim The JNK-dependent CaMK pathway restrains the reversion of committed cells during osteoclast differentiation J. Cell Sci., August 1, 2008; 121(15): 2555 - 2564. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Lorenzo, M. Horowitz, and Y. Choi Osteoimmunology: Interactions of the Bone and Immune System Endocr. Rev., June 1, 2008; 29(4): 403 - 440. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
