The effect of hemopoietic growth factors on the generation of osteoclast-like cells in mouse bone marrow cultures.
Multinucleated cells containing tartrate-resistant acid phosphatase were produced in mouse bone marrow cultures in response to 1,25-dihydroxyvitamin D3. These cells resemble osteoclasts in their morphology, possess receptors for calcitonin, and resorb bone in culture. The effects of several hemopoietic regulatory proteins on the generation of these cells were examined in this study. Interleukin-3, granulocyte-macrophage-stimulating factor (GMCSF), and macrophage-stimulating factor strongly inhibited generation of the tartrate-resistant acid phosphatase-containing multinucleated cells with approximate EC50 values of 3, 6, and 3 colony-forming units/ml, respectively. Granulocyte colony stimulating factor, interleukin-6, and leukemia inhibitory factor had no effect on the generation of these cells. In addition, we observed that the number of these cells was reduced when the bone marrow was plated at high cell density, and that this inhibitory effect was reversed by the addition of neutralizing antibodies directed against GMCSF. These findings suggest that GMCSF and other hemopoietic factors secreted by cells in the bone marrow regulate development of the osteoclast-like cells, possibly by diverting common precursor cells to alternate pathways.
Department of Bone Biology and Osteoporosis Research, Merck, Sharp, and Dohme Research Laboratories, West Point, Pennsylvania 19486.
D M
DM
Shinar
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M
Sato
G A
GA
Rodan
D000135:Acid Phosphatase / Q000378:metabolism; D000818:Animals; D000906:Antibodies / Q000276:immunology / Q000502:physiology; D001853:Bone Marrow / Q000378:metabolism; D001854:Bone Marrow Cells; D002116:Calcitonin / Q000378:metabolism; D002452:Cell Count; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D003115:Colony-Stimulating Factors / Q000276:immunology; D004351:Drug Resistance; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D006133:Growth Substances / Q000276:immunology / Q000494:pharmacology*; D006410:Hematopoiesis / Q000502:physiology*; D051379:Mice; D010010:Osteoclasts / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D013644:Tartrates / Q000494:pharmacology
D000906:Antibodies; D003115:Colony-Stimulating Factors; D006133:Growth Substances; D013644:Tartrates; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D002116:Calcitonin; D000135:Acid Phosphatase; C029768:tartaric acid