Abstract
Recently, receptor activator of NF-kappaB ligand (RANKL) was shown to be necessary for osteoclast formation. We now report that activin A, a cytokine enriched in bone matrix and secreted by osteoblasts and osteoclasts, powerfully synergized with RANKL for induction of osteoclast-like cells (OCL) from bone marrow precursors depleted of stromal cells. Moreover, OCL formation in RANKL was virtually abolished by soluble type II A activin receptors (ActR-II(A)), suggesting that activin A is essential for OCL formation. Activin A was most effective when precursors were exposed to RANKL and activin A simultaneously: resistance to OCL-induction that occurs when precursors are pre-incubated in M-CSF was reduced. Incubation on bone matrix also enhanced the sensitivity of precursors to OCL-induction by RANKL; and this was prevented by soluble ActR-II(A). Thus, activin A in bone matrix, or released from osteoblastic or other cells, enhances the osteoclast-forming potential of precursors and synergizes with RANKL in inducing osteoclastic differentiation.
Copyright 2000 Academic Press.
MeSH terms
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Activin Receptors, Type II
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Activins
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Animals
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Carrier Proteins / administration & dosage
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Carrier Proteins / pharmacology
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Carrier Proteins / physiology
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Cell Differentiation / drug effects
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Cell Differentiation / physiology
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Cells, Cultured
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Drug Synergism
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Hematopoietic Stem Cells / cytology
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Hematopoietic Stem Cells / drug effects
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Hematopoietic Stem Cells / physiology
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Inhibins / administration & dosage
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Inhibins / pharmacology
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Inhibins / physiology*
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Macrophage Colony-Stimulating Factor / administration & dosage
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Macrophage Colony-Stimulating Factor / pharmacology
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Membrane Glycoproteins / administration & dosage
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Membrane Glycoproteins / pharmacology
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Membrane Glycoproteins / physiology
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Mice
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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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Receptor Activator of Nuclear Factor-kappa B
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Receptors, Growth Factor / physiology
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Recombinant Proteins / administration & dosage
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Recombinant Proteins / pharmacology
Substances
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Carrier Proteins
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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, Growth Factor
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Recombinant Proteins
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Tnfrsf11a protein, mouse
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Tnfsf11 protein, mouse
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Activins
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Inhibins
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Macrophage Colony-Stimulating Factor
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Activin Receptors, Type II