Abstract
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.
Copyright 2001 Academic Press.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, Non-P.H.S.
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Animals, Newborn
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Bone Marrow Cells / cytology*
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Bone Marrow Cells / drug effects
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Carrier Proteins / pharmacology
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Cell Differentiation / drug effects
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Cells, Cultured
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Estrogen Receptor alpha
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Estrogen Receptor beta
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Gene Expression Regulation / drug effects
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Humans
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Kinetics
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Macrophage Colony-Stimulating Factor / pharmacology*
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Membrane Glycoproteins / pharmacology
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Osteoblasts / cytology*
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Osteoblasts / drug effects
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Osteoblasts / physiology
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Osteoclasts / cytology*
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Osteoclasts / drug effects
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Osteoclasts / physiology
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RANK Ligand
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Rats
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Rats, Sprague-Dawley
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Rats, Wistar
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Receptor Activator of Nuclear Factor-kappa B
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Receptors, Estrogen / genetics
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Recombinant Proteins / pharmacology
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Reverse Transcriptase Polymerase Chain Reaction
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Time Factors
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Transcription, Genetic / drug effects
Substances
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Carrier Proteins
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Estrogen Receptor alpha
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Estrogen Receptor beta
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Membrane Glycoproteins
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RANK Ligand
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Receptor Activator of Nuclear Factor-kappa B
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Receptors, Estrogen
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Recombinant Proteins
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TNFRSF11A protein, human
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TNFSF11 protein, human
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Macrophage Colony-Stimulating Factor