Abstract
The precise mechanism of how TNF-α promotes osteoclast formation is not clear. Previous reports show TNF-α targets molecules that regulate calcium signaling. Inositol-1,4,5-trisphosphate receptors (IP3Rs) are important calcium channel responsible for evoking intracellular calcium oscillation. We found that TNF-α increased the expression of IP3R1 and promoted osteoclastogenesis in RANKL-induced mouse BMMs. Phosphatidylcholine-specific phospholipase C (PC-PLC) specific inhibitor D609 eliminated the upregulation of IP3R1 by TNF-α, and decreased the autoamplification of nuclear factor of activated T-cells 1 (NFATc1), thus resulted in less osteoclasts formation. However, D609 did not inhibit RANKL-induced osteoclastogenesis. Our data suggest TNF-α promotes RANKL-induced osteoclastogenesis, at least partially, through PC-PLC/IP3R1/NFATc1 pathway.
Copyright © 2012 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Base Sequence
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Bone Marrow Cells / cytology
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Bone Marrow Cells / drug effects
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Bone Marrow Cells / metabolism
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Bone Resorption / etiology
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Bone Resorption / metabolism
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Bone Resorption / pathology
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Bridged-Ring Compounds / pharmacology
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Calcium Signaling / drug effects
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Cell Differentiation / drug effects
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Cell Differentiation / physiology
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DNA Primers / genetics
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Inositol 1,4,5-Trisphosphate Receptors / genetics
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Inositol 1,4,5-Trisphosphate Receptors / metabolism*
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Mice
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NFATC Transcription Factors / metabolism
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Norbornanes
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Osteoclasts / cytology
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Osteoclasts / drug effects
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Osteoclasts / metabolism*
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Phosphodiesterase Inhibitors / pharmacology
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RANK Ligand / metabolism
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Reactive Oxygen Species / metabolism
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Thiocarbamates
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Thiones / pharmacology
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Tumor Necrosis Factor-alpha / metabolism
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Tumor Necrosis Factor-alpha / pharmacology*
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Type C Phospholipases / antagonists & inhibitors
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Type C Phospholipases / metabolism*
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Up-Regulation / drug effects
Substances
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Bridged-Ring Compounds
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DNA Primers
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Inositol 1,4,5-Trisphosphate Receptors
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NFATC Transcription Factors
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Nfatc1 protein, mouse
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Norbornanes
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Phosphodiesterase Inhibitors
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RANK Ligand
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Reactive Oxygen Species
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Thiocarbamates
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Thiones
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Tnfsf11 protein, mouse
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Tumor Necrosis Factor-alpha
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tricyclodecane-9-yl-xanthogenate
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Type C Phospholipases
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phosphatidylcholine-specific phospholipase C