|
|
Blood, 1 May 2007, Vol. 109, No. 9, pp. 3839-3848.
Prepublished online as a Blood First Edition Paper on January 3, 2007; DOI 10.1182/blood-2006-07-037994.
 Previous Article | Table of Contents | Next Article 
IMMUNOBIOLOGY
B cells and T cells are critical for the preservation of bone homeostasis and attainment of peak bone mass in vivo
Yan Li1,
Gianluca Toraldo2,
Aimin Li1,
Xiaoying Yang1,
Hongying Zhang1,
Wei-Ping Qian1, and
M. Neale Weitzmann1
1 Division of Endocrinology & Metabolism & Lipids, Emory University School of Medicine, Atlanta, GA;
2 Department of Internal Medicine, Section of Internal Medicine and Endocrine and Metabolic Sciences, University of Perugia, Italy
Bone homeostasis is regulated by a delicate balance between osteoblastic bone formation and osteoclastic bone resorption. Osteoclastogenesis is controlled by the ratio of receptor activator of NF- B ligand (RANKL) relative to its decoy receptor, osteoprotegerin (OPG). The source of OPG has historically been attributed to osteoblasts (OBs). While activated lymphocytes play established roles in pathological bone destruction, no role for lymphocytes in basal bone homeostasis in vivo has been described. Using immunomagnetic isolation of bone marrow (BM) B cells and B-cell precursor populations and quantitation of their OPG production by enzyme-linked immunosorbent assay (ELISA) and real-time reverse transcriptase–polymerase chain reaction (RT-PCR), cells of the B lineage were found to be responsible for 64% of total BM OPG production, with 45% derived from mature B cells. Consistently B-cell knockout (KO) mice were found to be osteoporotic and deficient in BM OPG, phenomena rescued by B-cell reconstitution. Furthermore, T cells, through CD40 ligand (CD40L) to CD40 costimulation, promote OPG production by B cells in vivo. Consequently, T-cell–deficient nude mice, CD40 KO mice, and CD40L KO mice display osteoporosis and diminished BM OPG production. Our data suggest that lymphocytes are essential stabilizers of basal bone turnover and critical regulators of peak bone mass in vivo.
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
This article has been cited by other articles:
|
|
|
|
 
A. V. Sauer, E. Mrak, R. Jofra Hernandez, E. Zacchi, F. Cavani, M. Casiraghi, E. Grunebaum, C. M. Roifman, M. C. Cervi, A. Ambrosi, et al.
ADA-deficient SCID is associated with a specific microenvironment and bone phenotype characterized by RANKL/OPG imbalance and osteoblast insufficiency
Blood,
October 8, 2009;
114(15):
3216 - 3226.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. ELEFTHERIADIS, G. ANTONIADI, V. LIAKOPOULOS, and G. GALAKTIDOU
The Effect of Paricalcitol on Osteoprotegerin Production by Human Peripheral Blood Mononuclear Cells
J Rheumatol,
April 1, 2009;
36(4):
856 - 856.
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Ferrari-Lacraz and S. Ferrari
Effects of RANKL Inhibition on Inflammation and Immunity
IBMS BoneKEy,
March 1, 2009;
6(3):
116 - 126.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Pata, C. Heraud, and J. Vacher
OSTM1 Bone Defect Reveals an Intercellular Hematopoietic Crosstalk
J. Biol. Chem.,
November 7, 2008;
283(45):
30522 - 30530.
[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]
|
|
|
|
|
|
|
H K Datta, W F Ng, J A Walker, S P Tuck, and S S Varanasi
The cell biology of bone metabolism
J. Clin. Pathol.,
May 1, 2008;
61(5):
577 - 587.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. Galli, L. A. Zella, J. A. Fretz, Q. Fu, J. W. Pike, R. S. Weinstein, S. C. Manolagas, and C. A. O'Brien
Targeted Deletion of a Distant Transcriptional Enhancer of the Receptor Activator of Nuclear Factor-{kappa}B Ligand Gene Reduces Bone Remodeling and Increases Bone Mass
Endocrinology,
January 1, 2008;
149(1):
146 - 153.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
