RRC ID 51766
Author Iwazaki K, Tanaka T, Hozumi Y, Okada M, Tsuchiya R, Iseki K, Topham MK, Kawamae K, Takagi M, Goto K.
Title DGKζ Downregulation Enhances Osteoclast Differentiation and Bone Resorption Activity Under Inflammatory Conditions.
Journal J. Cell. Physiol.
Abstract Bone homeostasis is maintained by a balance between resorption of the bone matrix and its replacement by new bone. Osteoclasts play a crucially important role in bone metabolism. They are responsible for bone resorption under pathophysiological conditions. Differentiation of these cells, which are derived from bone marrow cells, depends on receptor activator of NF-κB ligand (RANKL). RANKL-induced osteoclastogenesis is regulated by the phosphoinositide (PI) signaling pathway, in which diacylglycerol (DG) serves as a second messenger in signal transduction. In this study, we examined the functional implications of DG kinase (DGK), an enzyme family responsible for DG metabolism, for osteoclast differentiation and activity. Of DGKs, DGKζ is most abundantly expressed in osteoclast precursors such as bone marrow-derived monocytes/macrophages. During osteoclast differentiation from precursor cells, DGKζ is downregulated at the protein level. In this regard, we found that DGKζ deletion enhances osteoclast differentiation and bone resorption activity under inflammatory conditions in an animal model of osteolysis. Furthermore, DGKζ deficiency upregulates RANKL expression in response to TNFα stimulation. Collectively, results suggest that DGKζ is silent under normal conditions, but it serves as a negative regulator in osteoclast function under inflammatory conditions. Downregulation of DGKζ might be one factor predisposing a person to osteolytic bone destruction in pathological conditions. J. Cell. Physiol. 232: 617-624, 2017. © 2016 Wiley Periodicals, Inc.
Volume 232(3)
Pages 617-624
Published 2017-3
DOI 10.1002/jcp.25461
PMID 27312515
MeSH Animals Biomarkers / metabolism Bone Density / drug effects Bone Resorption / complications Bone Resorption / enzymology* Bone Resorption / pathology* Cell Differentiation* / drug effects Diacylglycerol Kinase / metabolism* Disease Models, Animal Down-Regulation* Fibroblasts / metabolism Inflammation / complications Inflammation / enzymology Inflammation / pathology* Isoenzymes / metabolism Macrophages / drug effects Macrophages / metabolism Mice, Knockout Osteoclasts / drug effects Osteoclasts / pathology* Osteolysis / complications Osteolysis / enzymology Osteolysis / pathology RANK Ligand / genetics RANK Ligand / metabolism RNA, Messenger / genetics RNA, Messenger / metabolism Time Factors Tomography, X-Ray Computed Tumor Necrosis Factor-alpha / pharmacology Up-Regulation / drug effects
IF 4.522
Human and Animal Cells RAW 264(RCB0535)