We provide the first evidence that the bone marrow-derived cytokine, macrop
hage colony-stimulating factor (M-CSF), inhibits the formation of bone-form
ing osteoblasts, We examined both osteoclast and osteoblast formation in pr
imary rat bone marrow cultures. As expected, M-CSF together with osteoprote
gerin ligand (OPGL) markedly accelerated osteoclastogenesis, In contrast, t
reatment with M-CSF alone yielded no osteoclasts at any time. The most stri
king and novel observation was that M-CSF with or without OPGL dramatically
suppressed osteoblast formation. In separate experiments, estradiol marked
ly suppressed osteoclast formation in the M-CSF/OPGL-treated cultures indep
endently of osteoblasts, Consistent with this was the expression of estroge
n receptor-alpha (ER alpha) and ERP mRNA in osteoclast precursors. We there
fore conclude that in addition to the well-known action of M-CSF to modulat
e osteoclastogenesis, this cytokine may also regulate osteoblast formation.
(C) 2001 Academic Press.