The effects of several diphosphonates on murine bone marrow proliferation.
Six diphosphonates were examined for their ability to alter proliferative responses of mouse bone marrow cells to recombinant human M-CSF and recombinant murine GM-CSF. Risedronate ([2-(3-pyridinyl)-ethylidene] hydroxy bisphosphonic acid) added to in vitro cultures at 10 microM, suppressed the response to M-CSF by 58%, but had no significant effect on GM-CSF-induced proliferation. Ethane-1-hydroxy-1,1-bisphosphonic acid (EHDP), dichloromethylene bisphosphonic acid (Cl2MBP), 3-amino-1-hydroxy-propylidene-1,1-bisphosphonic acid (APD), (4-chlorophenyl)-thiomethylene bisphosphonic acid (tiludronate) and (cycloheptylamino)-methylene bisphosphonic acid (YM-175) had no significant effect. Treatment of mice for 5 or 14 days with 200 mg/kg/day p.o., Cl2MBP or 3 mg/kg/day p.o. of risedronate failed to inhibit M-CSF- or GM-CSF-induced proliferation by recovered bone marrow cells. Addition of Cl2MBP or risedronate in vitro to these cells did not reveal any change in sensitivity to CSFs as a result of exposure to diphosphonate in vivo.
Richard
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Department of Hypersensitivity Diseases Research, Upjohn Laboratories, Kalamazoo, MI 49001.
Staite
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D000818:Animals; D001853:Bone Marrow / Q000187:drug effects*; D001854:Bone Marrow Cells; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D004164:Diphosphonates / Q000494:pharmacology*; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology*; D016173:Macrophage Colony-Stimulating Factor / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D011994:Recombinant Proteins / Q000494:pharmacology
D004164:Diphosphonates; D011994:Recombinant Proteins; D016173:Macrophage Colony-Stimulating Factor; D016178:Granulocyte-Macrophage Colony-Stimulating Factor