title: PC-PLC is involved in osteoclastogenesis induced by TNF-α through upregulating IP3R1 expression.
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.
authors: Institution of Dental Medicine, Shandong University, Jinan 250012, PR China.
authors: Lin
authors: L
authors: Xia
authors: Dongyan
authors: D
authors: Zhang
authors: Chune
authors: C
authors: Wang
authors: Fengcai
authors: F
authors: Wei
authors: Yingwei
authors: Y
authors: Hu
mesh_terms: D000818:Animals; D001483:Base Sequence; D001854:Bone Marrow Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D001862:Bone Resorption / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D001952:Bridged-Ring Compounds / Q000494:pharmacology; D020013:Calcium Signaling / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D017931:DNA Primers / Q000235:genetics; D053496:Inositol 1,4,5-Trisphosphate Receptors / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D050778:NFATC Transcription Factors / Q000378:metabolism; D009636:Norbornanes; D010010:Osteoclasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D053245:RANK Ligand / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D013859:Thiocarbamates; D013871:Thiones / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism / Q000494:pharmacology*; D010738:Type C Phospholipases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D001952:Bridged-Ring Compounds; D017931:DNA Primers; D053496:Inositol 1,4,5-Trisphosphate Receptors; D050778:NFATC Transcription Factors; C494005:Nfatc1 protein, mouse; D009636:Norbornanes; D010726:Phosphodiesterase Inhibitors; D053245:RANK Ligand; D017382:Reactive Oxygen Species; D013859:Thiocarbamates; D013871:Thiones; C505689:Tnfsf11 protein, mouse; D014409:Tumor Necrosis Factor-alpha; C046498:tricyclodecane-9-yl-xanthogenate; D010738:Type C Phospholipases; C105598:phosphatidylcholine-specific phospholipase C