Journal
BRITISH JOURNAL OF HAEMATOLOGY
Volume 126, Issue 4, Pages 475-486Publisher
WILEY
DOI: 10.1111/j.1365-2141.2004.05084.x
Keywords
apoptosis; cytokines; myeloma bone disease; plasma cells; osteoblasts
Categories
Ask authors/readers for more resources
Bone remodelling is severely affected in myeloma bone disease as a consequence of skeletal metastatization of malignant plasma cells. We investigated whether defective bone replacement is dependent on increased osteoblast apoptosis and/or on deregulated events within the bone microenvironment. Circulating tumour necrosis factor (TNF)-alpha, interferon-gamma, interleukin (IL)-1beta, and IL-6 levels were higher in myeloma patients with overt bone disease, whose osteoblasts constitutively overexpressed Fas, DR4/DR5 complex as receptors to TNF-related apoptosis inducing ligand, intercellular adhesion molecule-1 (ICAM-1), and monocyte chemotactic protein-1 (MCP-1). They were functionally exhausted and promptly underwent apoptosis in vitro, in contrast to the minor tendency to death detected in control osteoblasts from patients without bone involvement and normal donors. Osteoblasts dramatically enhanced their apoptosis in co-cultures with MCC-2 myeloma cells and upregulated both ICAM-1 and MCP-1 in a manner similar to control osteoblasts. Pretreating MCC-2 cells with soluble ICAM-1 led to a striking inhibition of their adhesion to osteoblasts, suggesting that the ICAM-1/lymphocyte function-associated antigen-1 system plays a role in the reciprocal membrane contact to trigger apoptogenic signals. Our data suggest that, in the myeloma bone microenvironment, both high cytokine levels and physical interaction of malignant plasma cells with osteoblasts drive the accelerated apoptosis in these cells leading to defective new bone formation.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available