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Am J Physiol Endocrinol Metab 269: E1024-E1030, 1995;
0193-1849/95 $5.00
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AJP - Endocrinology and Metabolism, Vol 269, Issue 6 E1024-E1030, Copyright © 1995 by American Physiological Society

ARTICLES

Local concentrations of macrophage colony-stimulating factor mediate osteoclastic differentiation

S. L. Perkins and S. J. Kling
Department of Pathology, University of Utah School of Medicine, Salt Lake City 84132, USA.

Macrophage colony-stimulating factor (M-CSF) is essential for differentiation of osteoclasts and macrophages from a common bone marrow precursor. Using ST-2 stromal cell/murine bone marrow coculture, we studied the effects of increasing amounts of M-CSF on differentiation of macrophages and osteoclasts. Addition of exogenous M-CSF caused a dose-dependent 98% decrease in tartrate-resistant acid phosphatase (TRAP)-positive multinucleated cells, accompanied by a 2.5-fold increase in nonspecific esterase-staining macrophages. Similar decrease in osteoclastic functional activity, including 125I-labeled calcitonin binding and calcitonin-stimulated adenosine 3',5'-cyclic monophosphate (cAMP) production, were observed. Addition of exogenous M-CSF beyond 6 days in coculture had a decreasing ability to inhibit osteoclast formation, suggesting that M-CSF exerts its effects early in osteoclast differentiation, during the proposed proliferative phase of osteoclast formation. Similarly, early addition of neutralizing anti-M-CSF inhibited osteoclast formation, with diminishing effects beyond day 9. These results suggest that local high concentrations of M-CSF may influence the early determination of terminal differentiation into either macrophages or osteoclasts.


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