|
|
Blood, 15 August 2005, Vol. 106, No. 4, pp. 1407-1414.
Prepublished online as a Blood First Edition Paper on May 5, 2005; DOI 10.1182/blood-2005-03-1080.
 Previous Article | Table of Contents | Next Article 
NEOPLASIA
IL-3 is a potential inhibitor of osteoblast differentiation in multiple myeloma
Lori A. Ehrlich,
Ho Yeon Chung,
Irene Ghobrial,
Sun Jin Choi,
Francesca Morandi,
Simona Colla,
Vittorio Rizzoli,
G. David Roodman, and
Nicola Giuliani
From the Department of Medicine, University of Pittsburgh, PA; Veterans Affairs (VA)-Pittsburgh Medical Center, PA; and Cattedra di Ematologia, Universita Degli Studi di Parma, Italy.
Bone destruction in multiple myeloma is characterized both by markedly increased osteoclastic bone destruction and severely impaired osteoblast activity. We reported that interleukin-3 (IL-3) levels are increased in bone marrow plasma of myeloma patients compared with healthy controls and that IL-3 stimulates osteoclast formation. However, the effects of IL-3 on osteoblasts are unknown. Therefore, to determine if IL-3 inhibits osteoblast growth and differentiation, we treated primary mouse and human marrow stromal cells with IL-3 and assessed osteoblast differentiation. IL-3 inhibited basal and bone morphogenic protein-2 (BMP-2)-stimulated osteoblast formation in a dose-dependent manner without affecting cell growth. Importantly, marrow plasma from patients with high IL-3 levels inhibited osteoblast differentiation, which could be blocked by anti-IL-3. However, IL-3 did not inhibit osteoblast differentiation of osteoblastlike cell lines. In contrast, IL-3 increased the number of CD45+ hematopoietic cells in stromal-cell cultures. Depletion of the CD45+ cells abolished the inhibitory effects of IL-3 on osteoblasts, and reconstitution of the cultures with CD45+ cells restored the capacity of IL-3 to inhibit osteoblast differentiation. These data suggest that IL-3 plays a dual role in the bone destructive process in myeloma by both stimulating osteoclasts and indirectly inhibiting osteoblast formation. (Blood. 2005;106:1407-1414)
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
This article has been cited by other articles:
|
|
|
|
 
E. Terpos, O. Sezer, P. I. Croucher, R. Garcia-Sanz, M. Boccadoro, J. San Miguel, J. Ashcroft, J. Blade, M. Cavo, M. Delforge, et al.
The use of bisphosphonates in multiple myeloma: recommendations of an expert panel on behalf of the European Myeloma Network
Ann. Onc.,
May 22, 2009;
(2009)
mdn796v1.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
O. Sezer
Myeloma Bone Disease: Recent Advances in Biology, Diagnosis, and Treatment
Oncologist,
March 1, 2009;
14(3):
276 - 283.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. Kirshner, K. J. Thulien, L. D. Martin, C. Debes Marun, T. Reiman, A. R. Belch, and L. M. Pilarski
A unique three-dimensional model for evaluating the impact of therapy on multiple myeloma
Blood,
October 1, 2008;
112(7):
2935 - 2945.
[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]
|
|
|
|
|
|
|
Y. Kannan-Hayashi, K. Okamura, S. Hattori, M. Kuwamura, E. Higuchi, H. Terayama, M. Moriyama, M. Mukamoto, M. Okada, Y. Ohsugi, et al.
Neuritogenic Effects of T Cell-Derived IL-3 on Mouse Splenic Sympathetic Neurons In Vivo
J. Immunol.,
March 15, 2008;
180(6):
4227 - 4234.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
E. Terpos, O. Sezer, P. Croucher, and M.-A. Dimopoulos
Myeloma bone disease and proteasome inhibition therapies
Blood,
August 15, 2007;
110(4):
1098 - 1104.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
N. Giuliani, F. Morandi, S. Tagliaferri, M. Lazzaretti, S. Bonomini, M. Crugnola, C. Mancini, E. Martella, L. Ferrari, A. Tabilio, et al.
The proteasome inhibitor bortezomib affects osteoblast differentiation in vitro and in vivo in multiple myeloma patients
Blood,
July 1, 2007;
110(1):
334 - 338.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. Standal, N. Abildgaard, U.-M. Fagerli, B. Stordal, O. Hjertner, M. Borset, and A. Sundan
HGF inhibits BMP-induced osteoblastogenesis: possible implications for the bone disease of multiple myeloma
Blood,
April 1, 2007;
109(7):
3024 - 3030.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Yaccoby, W. Ling, F. Zhan, R. Walker, B. Barlogie, and J. D. Shaughnessy Jr
Antibody-based inhibition of DKK1 suppresses tumor-induced bone resorption and multiple myeloma growth in vivo
Blood,
March 1, 2007;
109(5):
2106 - 2111.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
N. Giuliani, V. Rizzoli, and G. D. Roodman
Multiple myeloma bone disease: pathophysiology of osteoblast inhibition
Blood,
December 15, 2006;
108(13):
3992 - 3996.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
G. D. Roodman
New potential targets for treating myeloma bone disease.
Clin. Cancer Res.,
October 15, 2006;
12(20):
6270s - 6273s.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. N. Pearse
Wnt antagonism in multiple myeloma: a potential cause of uncoupled bone remodeling.
Clin. Cancer Res.,
October 15, 2006;
12(20):
6274s - 6278s.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
N. Giuliani, F. Morandi, S. Tagliaferri, S. Colla, S. Bonomini, G. Sammarelli, and V. Rizzoli
Interleukin-3 (IL-3) is overexpressed by T lymphocytes in multiple myeloma patients
Blood,
January 15, 2006;
107(2):
841 - 842.
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. Oshima, M. Abe, J. Asano, T. Hara, K. Kitazoe, E. Sekimoto, Y. Tanaka, H. Shibata, T. Hashimoto, S. Ozaki, et al.
Myeloma cells suppress bone formation by secreting a soluble Wnt inhibitor, sFRP-2
Blood,
November 1, 2005;
106(9):
3160 - 3165.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
