Abstract
Recent studies have revealed that both transforming growth factor-beta (TGF-beta) and activin A play pivotal roles in osteoclastogenesis. In this report, we show that the effect of TGF-beta family members, TGF-beta1 and activin A, but not BMP-2, enhance multinucleated osteoclast-like cell (OCL) formation induced by receptor activator of NF-kappaB ligand (RANKL) in isolated bone marrow macrophages and monocytic cell line, RAW264.7. TGF-beta1 and activin A caused the growth suppression and concomitant expression of tartrate-resistant acid phosphatase (TRAP) and c-Src, without inducing syncytium formation or increasing the survival rate in RAW264.7 cells. Although TGF-beta1 and activin A had no effect on NF-kappaB and JNK activities, these factors enhanced the expression of JunB, a component of the AP-1 transcriptional complex. These results suggest that TGF-beta1 and activin A may function as commitment factors in osteoclastic differentiation, not as a crucial component for terminal differentiation to form multinucleated OCLs nor in OCL survival.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Acid Phosphatase / metabolism
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Activins / pharmacology
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Activins / physiology*
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Animals
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Bone Marrow Cells / drug effects
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Bone Marrow Cells / physiology
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Bone Morphogenetic Protein 2
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Bone Morphogenetic Proteins / pharmacology
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Carrier Proteins / pharmacology*
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Cell Differentiation
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Cell Division / drug effects
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Cell Line
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Cell Survival
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Cells, Cultured
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Dose-Response Relationship, Drug
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Female
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Inhibin-beta Subunits / pharmacology
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Inhibin-beta Subunits / physiology*
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Isoenzymes / metabolism
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JNK Mitogen-Activated Protein Kinases
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Kinetics
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Membrane Glycoproteins / pharmacology*
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Mice
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Mitogen-Activated Protein Kinases / metabolism
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NF-kappa B / metabolism
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Osteoclasts / physiology*
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Proto-Oncogene Proteins pp60(c-src) / metabolism
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RANK Ligand
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Receptor Activator of Nuclear Factor-kappa B
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Tartrate-Resistant Acid Phosphatase
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Transforming Growth Factor beta / pharmacology
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Transforming Growth Factor beta / physiology*
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Transforming Growth Factor beta1
Substances
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Bmp2 protein, mouse
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Bone Morphogenetic Protein 2
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Bone Morphogenetic Proteins
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Carrier Proteins
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Isoenzymes
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Membrane Glycoproteins
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NF-kappa B
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RANK Ligand
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Receptor Activator of Nuclear Factor-kappa B
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Tgfb1 protein, mouse
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Tnfrsf11a protein, mouse
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Tnfsf11 protein, mouse
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Transforming Growth Factor beta
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Transforming Growth Factor beta1
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activin A
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Activins
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Inhibin-beta Subunits
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Proto-Oncogene Proteins pp60(c-src)
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JNK Mitogen-Activated Protein Kinases
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Mitogen-Activated Protein Kinases
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Acid Phosphatase
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Acp5 protein, mouse
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Tartrate-Resistant Acid Phosphatase