Effects of human recombinant CSF-GM and highly purified CSF-1 on the formation of multinucleated cells with osteoclast characteristics in long-term bone marrow cultures.
Several studies have suggested that the osteoclast is derived from a mononuclear precursor which is found in bone marrow. We have developed a system for studying the formation of osteoclast-like multinucleated cells in long-term bone marrow culture of baboon cells. Recombinant human CSF-GM and highly purified CSF-1, both of which stimulate the proliferation of monocyte/macrophage precursors, were found to increase the number of osteoclast-like cells formed in long-term bone marrow culture. CSF-GM stimulated multinucleated cell formation more consistently than CSF-1. The subsequent addition of 1,25-dihydroxyvitamin D3 (1,25-(OH)2D3) to cultures initially treated with CSF-GM or CSF-1 further increased multinucleated cell formation. Autoradiographic studies indicate that CSF stimulated multinucleated cell formation by increasing the proliferation of the precursor cell, and that the potentiating effect of 1,25-(OH)2D3 was caused by fusion of the increased numbers of precursors. These studies suggest that the interaction of locally produced colony-stimulating factors with circulating calcium regulating hormones may be important in the control of osteoclast formation and bone resorption.
MacDonald
B R
BR
Research Service, Audie Murphy Veterans Administration Hospital, San Antonio, TX.
Mundy
G R
GR
Clark
S
S
Wang
E A
EA
Kuehl
T J
TJ
Stanley
E R
ER
Roodman
G D
GD
D000818:Animals; D001345:Autoradiography; D001853:Bone Marrow / Q000187:drug effects*; D001854:Bone Marrow Cells; D002117:Calcitriol / Q000494:pharmacology; D003115:Colony-Stimulating Factors / Q000494:pharmacology*; D003470:Culture Media; D046508:Culture Techniques; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D006133:Growth Substances / Q000494:pharmacology*; D006801:Humans; D010010:Osteoclasts / Q000187:drug effects*; D010215:Papio; D011994:Recombinant Proteins / Q000494:pharmacology; D013997:Time Factors
D003115:Colony-Stimulating Factors; D003470:Culture Media; D006133:Growth Substances; D011994:Recombinant Proteins; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D002117:Calcitriol