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Macrophage colony stimulating factor down-regulates MCSF-receptor expression and entry of progenitors into the osteoclast lineage.

Authors
Type
Published Article
Journal
Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research
Publication Date
Volume
12
Issue
9
Pages
1387–1395
Identifiers
PMID: 9286754
Source
Medline
License
Unknown

Abstract

Macrophage colony-stimulating factor (MCSF), although necessary for entry of precursors into the early preosteoclast pathway, inhibits osteoclastogenesis at high doses. To clarify the relationship between MCSF and osteoclast formation, we investigated the effect of exogenous MCSF in murine bone marrow culture. Precursor proliferation and the expression of MCSF-receptor were examined after 4 days of culture in the presence or absence of accessory stromal cells. In both mixed marrow and destromalized cell cultures, exogenous MCSF dose-dependently decreased 125I-MCSF binding (by 65 +/- 5.0% at 3500 and 87 +/- 16.7% at-7000 U/ml, respectively) while enhancing mononuclear cell proliferation after 3 days of exposure (by 2.8- and 6.3-fold, respectively). These effects were maintained 24 h after removal of exogenous MCSF and, as such, likely represented an MCSF-induced change in MCSF receptor-bearing cells. Exposure to exogenous MCSF (3500 U/ml) days 2-4 dose-dependently inhibited tartrate resistant acid phosphatase positive multinuclear cell (TRAP+ MNC) formation counted at the end of day 7, by 64.3 +/- 4.1%. This inhibition of TRAP+ MNC formation was preceded by a 92 +/- 9% decrease in the expression of carbonic anhydrase II mRNA measurable at 4 days. These results indicate that MCSF promotes proliferation of a population of cells expressing lower cognate receptor sites. Changes in MCSF-receptor expression appear to modulate the final lineage selection of the pluripotent monoblastic progenitor.

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