Macrophage colony-stimulating factor suppresses osteoblast formation.
We provide the first evidence that the bone marrow-derived cytokine, macrophage colony-stimulating factor (M-CSF), inhibits the formation of bone-forming osteoblasts. We examined both osteoclast and osteoblast formation in primary rat bone marrow cultures. As expected, M-CSF together with osteoprotegerin ligand (OPGL) markedly accelerated osteoclastogenesis. In contrast, treatment with M-CSF alone yielded no osteoclasts at any time. The most striking and novel observation was that M-CSF with or without OPGL dramatically suppressed osteoblast formation. In separate experiments, estradiol markedly suppressed osteoclast formation in the M-CSF/OPGL-treated cultures independently of osteoblasts. Consistent with this was the expression of estrogen receptor-alpha (ERalpha) and ERbeta mRNA in osteoclast precursors. We therefore conclude that in addition to the well-known action of M-CSF to modulate osteoclastogenesis, this cytokine may also regulate osteoblast formation.
Gyda
M
M
Geriatric Research Education and Clinical Center, Bronx VA Medical Center, 130 West Kingsbridge Road, Bronx, NY 10468, USA.
Corisdeo
S
S
Zaidi
M
M
Troen
B R
BR
D000818:Animals; D000831:Animals, Newborn; D001854:Bone Marrow Cells / Q000166:cytology* / Q000187:drug effects; D002352:Carrier Proteins / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007700:Kinetics; D016173:Macrophage Colony-Stimulating Factor / Q000494:pharmacology*; D008562:Membrane Glycoproteins / Q000494:pharmacology; D010006:Osteoblasts / Q000166:cytology* / Q000187:drug effects / Q000502:physiology; D010010:Osteoclasts / Q000166:cytology* / Q000187:drug effects / Q000502:physiology; D053245:RANK Ligand; D051381:Rats; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D053246:Receptor Activator of Nuclear Factor-kappa B; D011960:Receptors, Estrogen / Q000235:genetics; D011994:Recombinant Proteins / Q000494:pharmacology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D014158:Transcription, Genetic / Q000187:drug effects
D002352:Carrier Proteins; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D008562:Membrane Glycoproteins; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; D011960:Receptors, Estrogen; D011994:Recombinant Proteins; C505686:TNFRSF11A protein, human; C505688:TNFSF11 protein, human; D016173:Macrophage Colony-Stimulating Factor