Bisphosphonates in vitro specifically inhibit, among the hematopoietic series, the development of the mouse mononuclear phagocyte lineage

Journal Article · Mon Oct 01 00:00:00 EDT 1990 · Journal of Bone and Mineral Research; (USA)

DOI:https://doi.org/10.1002/jbmr.5650051005· OSTI ID:5802268

Cecchini, M G; Fleisch, H ^[1]

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1. Univ. of Bern (Switzerland)

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.

• OSTI ID: 5802268
• Journal Information: Journal of Bone and Mineral Research; (USA), Vol. 5:10; ISSN 0884-0431
• Country of Publication: United States
• Language: English

Related Subjects

59 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
550201* - Biochemistry- Tracer Techniques