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Macrophage colony-stimulating factor induces substantial osteoclast
generation and bone resorption in human bone marrow cultures
U Sarma and AM Flanagan
Department of Histopathology, Imperial College School of Medicine at St.
Mary's, London, UK.
Macrophage colony-stimulating factor (M-CSF) is essential for murine
osteoclast formation and its role in human hematopoiesis in vitro is not
fully defined. Therefore, we have investigated the effect of M-CSF on the
formation of human osteoclasts in vitro. M-CSF was found to induce
substantial bone resorption and osteoclast formation in a dose- responsive
and time-dependent manner above that induced by 1,25 dihydroxyvitamin D3
(1,25 vitamin D3) in cultures of human bone marrow (BM) stromal cells
sedimented onto devitalized bone. By day 14 there was a mean of
approximately 50% of the surfaces of the bone slices resorbed compared with
only 6% in cultures treated with 1,25 vitamin D3 alone. Osteoclasts were
identified as 23c6+ cells (an antibody that recognizes the vitronectin
receptor), 87.5% of which coexpressed the calcitonin receptor. The number
of 23c6+ cells correlated strongly with bone resorption spatially, and in a
dose-responsive and time-dependent manner; the correlation coefficient in
cultures treated with 1,25 vitamin D3 alone was 0.856 and those treated
with both M-CSF and 1,25 vitamin D3 was 0.880. Granulocyte-macrophage
colony-stimulating factor, IL-1 beta, IL-3, IL-6, tumor necrosis
factor-alpha, transforming growth factor-beta, leukemia inhibitory factor,
and IL-11 did not increase bone resorption above that in 1,25 vitamin
D3-treated cultures. We also found that 1,25 vitamin D3 increased, to a
minor but significant degree, both bone resorption and the concentration of
M-CSF in the culture supernatants above that in vehicle-treated cultures,
indicating that M-CSF is present in our BM cultures, but that there is
insufficient to induce substantial osteoclast formation. These results
define a critical role for M-CSF in the formation of human osteoclasts.
Volume 88,
Issue 7,
pp. 2531-2540,
10/01/1996
Copyright © 1996 by The American Society of Hematology
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