| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
-Induced Osteoclastogenesis In Vivo1
Departments of
*
Pathology and Immunology,
Internal Medicine, and
Orthopedic Surgery, Washington University School of Medicine, St. Louis, MO 63110
The marrow stromal cell is the principal source of the key osteoclastogenic cytokine receptor activator of NF-
B (RANK) ligand (RANKL). To individualize the role of marrow stromal cells in varying states of TNF-
-driven osteoclast formation in vivo, we generated chimeric mice in which wild-type (WT) marrow, immunodepleted of T cells and stromal cells, is transplanted into lethally irradiated mice deleted of both the p55 and p75 TNFR. As control, similarly treated WT marrow was transplanted into WT mice. Each group was administered increasing doses of TNF-. Exposure to high-dose cytokine ex vivo induces exuberant osteoclastogenesis irrespective of in vivo TNF- treatment or whether the recipient animals possess TNF--responsive stromal cells. In contrast, the osteoclastogenic capacity of marrow treated with lower-dose TNF- requires priming by TNFR-bearing stromal cells in vivo. Importantly, the osteoclastogenic contribution of cytokine responsive stromal cells in vivo diminishes as the dose of TNF- increases. In keeping with this conclusion, mice with severe inflammatory arthritis develop profound osteoclastogenesis and bone erosion independent of stromal cell expression of TNFR. The direct induction of osteoclast recruitment by TNF- is characterized by enhanced RANK expression and sensitization of precursor cells to RANKL. Thus, osteolysis attending relatively modest elevations in ambient TNF- depends upon responsive stromal cells. Alternatively, in states of severe periarticular inflammation, TNF- may fully exert its bone erosive effects by directly promoting the differentiation of osteoclast precursors independent of cytokine-responsive stromal cells and T lymphocytes.
This article has been cited by other articles:
|
|
 |
|
  T. K. Sampath, P. Simic, S. Moreno, N. Bukanov, N. Draca, V. Kufner, A. Tikvica, A. Blair, D. Semenski, M. Brncic, et al. Sevelamer Restores Bone Volume and Improves Bone Microarchitecture and Strength in Aged Ovariectomized Rats Endocrinology, December 1, 2008; 149(12): 6092 - 6102. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Kitaura, M. Yoshimatsu, Y. Fujimura, T. Eguchi, H. Kohara, A. Yamaguchi, and N. Yoshida An Anti-c-Fms Antibody Inhibits Orthodontic Tooth Movement Journal of Dental Research, April 1, 2008; 87(4): 396 - 400. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Vaira, T. Johnson, A. C. Hirbe, M. Alhawagri, I. Anwisye, B. Sammut, J. O'Neal, W. Zou, K. N. Weilbaecher, R. Faccio, et al. RelB is the NF-{kappa}B subunit downstream of NIK responsible for osteoclast differentiation PNAS, March 11, 2008; 105(10): 3897 - 3902. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Angelucci, S. Garofalo, S. Speca, A. Bovadilla, G. L. Gravina, P. Muzi, C. Vicentini, and M. Bologna Arachidonic acid modulates the crosstalk between prostate carcinoma and bone stromal cells Endocr. Relat. Cancer, March 1, 2008; 15(1): 91 - 100. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 X. Li, L. Qin, M. Bergenstock, L. M. Bevelock, D. V. Novack, and N. C. Partridge Parathyroid Hormone Stimulates Osteoblastic Expression of MCP-1 to Recruit and Increase the Fusion of Pre/Osteoclasts J. Biol. Chem., November 9, 2007; 282(45): 33098 - 33106. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Ochi, M. Shinohara, K. Sato, H.-J. Gober, T. Koga, T. Kodama, T. Takai, N. Miyasaka, and H. Takayanagi Pathological role of osteoclast costimulation in arthritis-induced bone loss PNAS, July 3, 2007; 104(27): 11394 - 11399. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. E. Sprague, H. Kitaura, W. Zou, Y. Ye, S. Achilefu, K. N. Weilbaecher, S. L. Teitelbaum, and C. J. Anderson Noninvasive Imaging of Osteoclasts in Parathyroid Hormone-Induced Osteolysis Using a 64Cu-Labeled RGD Peptide J. Nucl. Med., February 1, 2007; 48(2): 311 - 318. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. L. Teitelbaum Osteoclasts: What Do They Do and How Do They Do It? Am. J. Pathol., February 1, 2007; 170(2): 427 - 435. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Zhou, H. Kitaura, S. L. Teitelbaum, G. Krystal, F. P. Ross, and S. Takeshita SHIP1 Negatively Regulates Proliferation of Osteoclast Precursors via Akt-Dependent Alterations in D-Type Cyclins and p27 J. Immunol., December 15, 2006; 177(12): 8777 - 8784. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Wang, P. R. Crisostomo, C. Herring, K. K. Meldrum, and D. R. Meldrum Human progenitor cells from bone marrow or adipose tissue produce VEGF, HGF, and IGF-I in response to TNF by a p38 MAPK-dependent mechanism Am J Physiol Regulatory Integrative Comp Physiol, October 1, 2006; 291(4): R880 - R884. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Z. Yao, P. Li, Q. Zhang, E. M. Schwarz, P. Keng, A. Arbini, B. F. Boyce, and L. Xing Tumor Necrosis Factor-{alpha} Increases Circulating Osteoclast Precursor Numbers by Promoting Their Proliferation and Differentiation in the Bone Marrow through Up-regulation of c-Fms Expression J. Biol. Chem., April 28, 2006; 281(17): 11846 - 11855. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
