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Author Cecchini, M. G. ♦ Fleisch, H.
Source United States Department of Energy Office of Scientific and Technical Information
Content type Text
Language English
Subject Keyword BASIC BIOLOGICAL SCIENCES ♦ MACROPHAGES ♦ CELL PROLIFERATION ♦ PHOSPHONATES ♦ BIOLOGICAL FUNCTIONS ♦ BONE CELLS ♦ BONE MARROW CELLS ♦ COLONY FORMATION ♦ DOSE-RESPONSE RELATIONSHIPS ♦ GROWTH FACTORS ♦ IN VITRO ♦ INHIBITION ♦ MICE ♦ SPLEEN ♦ THYMIDINE ♦ TRACER TECHNIQUES ♦ TRITIUM COMPOUNDS ♦ ANIMAL CELLS ♦ ANIMALS ♦ AZINES ♦ BODY ♦ CONNECTIVE TISSUE CELLS ♦ FUNCTIONS ♦ HETEROCYCLIC COMPOUNDS ♦ HYDROGEN COMPOUNDS ♦ ISOTOPE APPLICATIONS ♦ MAMMALS ♦ MITOGENS ♦ NUCLEOSIDES ♦ NUCLEOTIDES ♦ ORGANIC COMPOUNDS ♦ ORGANIC NITROGEN COMPOUNDS ♦ ORGANIC PHOSPHORUS COMPOUNDS ♦ ORGANS ♦ PHAGOCYTES ♦ PROTEINS ♦ PYRIMIDINES ♦ RIBOSIDES ♦ RODENTS ♦ SOMATIC CELLS ♦ VERTEBRATES ♦ Biochemistry- Tracer Techniques
Abstract Bisphosphonates (BP) are powerful inhibitors of bone resorption. We have previously shown that 4-amino-1-hydroxybutylidene-1,1-bisphosphonate (AHBuBP), 3-amino-1-hydroxypropylidene-1,1-bisphosphonate (AHPrBP), and dichloromethylenebisphosphonate (Cl2MBP) inhibit the proliferation of macrophages in vitro at concentrations that do not affect the viability of nonproliferating cells. In this study we further investigated whether the antiproliferative effect of these three BP is, among the hematopoietic series, preferential to the mononuclear phagocyte lineage. BP were unable to inhibit more than 30-40% of the ({sup 3}H)thymidine ({sup 3}H-TdR) incorporation into bone marrow cells stimulated to proliferate by multilineage colony-stimulating activity containing conditioned medium (multi-CSA). From the analysis of the colonies induced in semisolid medium by multi-CSA and recombinant murine granulocyte-macrophage colony stimulating factor (rmGM-CSF), a dose-dependent disappearance specific to the macrophage-containing colonies emerged. In contrast, the number and composition of colonies other than macrophage and, in particular, the granulocyte colonies were not affected by these compounds, even at high concentrations (100 microM) previously also shown to be toxic for nonproliferating macrophages. Since the macrophages, differently from polymorphonuclear phagocytes, are known to be highly pinocytotic, it is possible that by this means they selectively concentrate BP intracellularly, leading to toxic concentrations. We postulate tht BP may also act in vivo in addition to their effect on osteoclast activity, by a similar mechanism on osteoclast precursors and on bone resident macrophages, a source of cytokines stimulating bone resorption and leading to impaired osteoclast recruitment and activity.
ISSN 08840431
Educational Use Research
Learning Resource Type Article
Publisher Date 1990-10-01
Publisher Place United States
Journal Journal of Bone and Mineral Research
Volume Number 5
Issue Number 10


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