| First Author | Iwazaki K | Year | 2017 |
| Journal | J Cell Physiol | Volume | 232 |
| Issue | 3 | Pages | 617-624 |
| PubMed ID | 27312515 | Mgi Jnum | J:317038 |
| Mgi Id | MGI:6844223 | Doi | 10.1002/jcp.25461 |
| Citation | Iwazaki K, et al. (2017) DGKzeta Downregulation Enhances Osteoclast Differentiation and Bone Resorption Activity Under Inflammatory Conditions. J Cell Physiol 232(3):617-624 |
| abstractText | 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-kappaB 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, DGKzeta is most abundantly expressed in osteoclast precursors such as bone marrow-derived monocytes/macrophages. During osteoclast differentiation from precursor cells, DGKzeta is downregulated at the protein level. In this regard, we found that DGKzeta deletion enhances osteoclast differentiation and bone resorption activity under inflammatory conditions in an animal model of osteolysis. Furthermore, DGKzeta deficiency upregulates RANKL expression in response to TNFalpha stimulation. Collectively, results suggest that DGKzeta is silent under normal conditions, but it serves as a negative regulator in osteoclast function under inflammatory conditions. Downregulation of DGKzeta might be one factor predisposing a person to osteolytic bone destruction in pathological conditions. J. Cell. Physiol. 232: 617-624, 2017. (c) 2016 Wiley Periodicals, Inc. |
