Local concentrations of macrophage colony stimulating factor
mediate osteoclastic differentiation.
Perkins, Sherrie L., and Stephen J. Kling.
Department of Pathology, University of Utah School of Medicine,
Salt Lake City, UT 84132
APStracts 2:0140E, 1995.
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 co
-culture, 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 TRAP-positive
multinucleated cells, accompanied by a 2.5 fold increase in
nonspecific esterase staining macrophages. Similar decreases in
osteoclastic functional activity, including 125I-calcitonin binding
and calcitonin-stimulated cAMP production were observed. Addition of
exogenous M-CSF beyond 6 days in co-culture 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.
Received 27 March 1995; accepted in final form 23 June 1995.
APS Manuscript Number E141-5.
Article publication pending Am. J. Physiol. (Endocrinol. Metab.).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 11 July 1995.