Human Myeloma Cells Promote the Recruitment of Osteoblast Precursors: Mediation by Interleukin‐6 and Soluble Interleukin‐6 Receptor

Multiple myeloma is associated with the development of osteolytic bone disease characterized by a disruption to normal bone resorption and bone formation. Although studies have shown that myeloma cells produce factors that promote bone resorption little data are available examining the mechanism of...

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Bibliographic Details
Published in:Journal of bone and mineral research 2000-10, Vol.15 (10), p.1935-1943
Main Authors: Karadag, Abdullah, Scutt, Andrew M., Croucher, Peter I.
Format: Article
Language:English
Subjects:
Alkaline Phosphatase - metabolism
Antibodies - pharmacology
Biological and medical sciences
bone marrow stromal cell
Bone Remodeling - drug effects
Calcium - metabolism
Cell Count
Cell Differentiation - drug effects
Coculture Techniques
Collagen - metabolism
Culture Media, Conditioned - pharmacology
Humans
Immunodeficiencies. Immunoglobulinopathies
Immunoglobulinopathies
Immunopathology
Interleukin-6 - pharmacology
Interleukin-6 - secretion
interleukin‐6
interleukin‐6 receptor
Medical sciences
Mesoderm - cytology
Mesoderm - drug effects
multiple myeloma
Multiple Myeloma - pathology
Multiple Myeloma - secretion
osteoblast
Osteoblasts - cytology
Osteoblasts - drug effects
Osteoblasts - enzymology
Osteoblasts - metabolism
Receptors, Interleukin-6 - administration & dosage
Receptors, Interleukin-6 - antagonists & inhibitors
Receptors, Interleukin-6 - metabolism
Solubility
Stem Cells - cytology
Stem Cells - drug effects
Stem Cells - enzymology
Stem Cells - metabolism
Tetradecanoylphorbol Acetate - pharmacology
Tumor Cells, Cultured
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Summary:Multiple myeloma is associated with the development of osteolytic bone disease characterized by a disruption to normal bone resorption and bone formation. Although studies have shown that myeloma cells produce factors that promote bone resorption little data are available examining the mechanism of decreased bone formation or the factors that mediate this effect. In the present study we describe a novel in vitro coculture system in which to investigate the effect of myeloma cells on osteoblast recruitment and differentiation. Under appropriate conditions mesenchymal stem cells were shown to differentiate into colonies of cells, a proportion of which show characteristics of osteoblasts, in that they express alkaline phosphatase activity and stain positively for collagen and calcium. The addition of the human myeloma cells JJN‐3, RPMI‐8226, or NCI‐H929 to these cultures stimulated a significant increase in the total number of colonies (p < 0.005) and the proportion of osteoblastic colonies (p < 0.005). Media conditioned by these cells also were able to promote the formation of both total and osteoblastic colonies (p < 0.005). The addition of an antibody against the interleukin‐6 receptor (IL‐6R) blocked myeloma cell and myeloma cell‐conditioned media induced osteoblast recruitment (p < 0.01). Furthermore, media conditioned by myeloma cells incubated with phorbol ester, which promotes IL‐6R shedding, or a metalloproteinase inhibitor, which inhibits IL‐6R shedding, were able to stimulate (p < 0.005) and inhibit osteoblast recruitment (p < 0.005), respectively. In addition, soluble IL‐6R (sIL‐6R) and IL‐6 together, but not alone, were able to promote osteoblastic colony formation (p < 0.01). Taken together these data show that myeloma cells promote osteoblast recruitment by release of sIL‐6R from myeloma cells.
ISSN:0884-0431
1523-4681
DOI:10.1359/jbmr.2000.15.10.1935