Title
A murine model of human myeloma bone disease
Author
Garrett, I.R.
Dallas, S.
Radl, J.
Mundy, G.R.
TNO Preventie en Gezondheid
Publication year
1997
Abstract
Myeloma causes a devastating and unique form of osteolytic bone disease. Although osteoclast activation is responsible for bone destruction, the precise mechanisms by which myeloma cells increase osteoclast activity have not been defined. An animal model of human myeloma bone disease mould help in clarification of these mechanisms. Multiple myeloma occurs spontaneously in aging C57 BL/KaLwRij mice and has all of the features of the disease in humans, including the characteristic bone lesions. The disease can be induced in normal C57 BL/KaLwRij mice by inoculation of fresh marrow-derived cells from mice with myeloma, but this model is difficult to study because of variability in the number of myeloma cells in marrow-derived preparations. To develop a better animal model of human myeloma bone disease, we have established and subcloned a cell line from this murine myeloma and found that it causes osteolytic bone lesions in mice characteristic of human myeloma bone disease. The cell line produces interleukin-6, but grows independent of exogenous interleukin-6. Mice inoculated intravenously with the cultured cells predictably develop an identical disease to the mice injected intravenously with fresh bone-marrow-derived myeloma cells, including monoclonal gammopathy and radiologic bone lesions. We found that some of the mice became hypercalcemic, and the bone lesions are characterized by increased osteoclast activity. We found identical results when we inoculated Nu/Bg/XID mice with cultured murine myeloma cells. Because we can inoculate mice with precise numbers of cells and predict accurately when the mice will develop bone lesions, become hypercalcemic, and die, this should be a convenient model for determining the mechanisms by which the myeloma cells cause osteoclast activation in this model of human myeloma bone disease.
Subject
Health
Bone
Hypercalcemia
Interleukin-6
Myeloma
Osteoclasts
Osteolysis
Animals
Bone Marrow
Bone Marrow Transplantation
Bone Neoplasms
Calcium
Cell Division
Disease Models, Animal
Femur
Humans
Immunocompromised Host
Immunoglobulin G
Mice
Mice, Inbred C57BL
Mice, Nude
Multiple Myeloma
Tumor Cells, Cultured
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DOI
https://doi.org/10.1016/s8756-3282(97)00056-2
TNO identifier
233929
ISSN
8756-3282
Source
Bone, 20 (6), 515-520
Document type
article