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Macrophage Colony Stimulating Factor Down‐Regulates MCSF‐Receptor Expression and Entry of Progenitors into the Osteoclast Lineage
Author(s) -
Fan Xian,
Biskobing Diane M.,
Fan Dongjie,
Hofstetter Willy,
Rubin Janet
Publication year - 1997
Publication title -
journal of bone and mineral research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.882
H-Index - 241
eISSN - 1523-4681
pISSN - 0884-0431
DOI - 10.1359/jbmr.1997.12.9.1387
Subject(s) - macrophage colony stimulating factor , receptor , osteoclast , stromal cell , microbiology and biotechnology , progenitor cell , endocrinology , medicine , population , colony stimulating factor , chemistry , biology , macrophage , haematopoiesis , cancer research , biochemistry , stem cell , in vitro , environmental health
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 125 I‐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.