論文 - 詳細
| RRC ID | 61226 |
|---|---|
| 著者 | Hikiji H, Ishii S, Shindou H, Takato T, Shimizu T. |
| タイトル | Absence of platelet-activating factor receptor protects mice from osteoporosis following ovariectomy. |
| ジャーナル | J Clin Invest |
| Abstract |
While platelet-activating factor (PAF) is produced in various diseases associated with bone resorption, its functions in bone metabolism remain unknown. Using PAF receptor-deficient mice, we evaluated the role of PAF in the development of bone resorption following ovariectomy, a model of postmenopausal osteoporosis. Through observations of bone mineral density and histomorphometric parameters, it was found that bone resorption was markedly attenuated in PAF receptor-deficient mice, indicating that PAF links estrogen depletion and osteoporosis in vivo. Osteoclasts expressed higher amounts of the enzymes required for PAF biosynthesis than osteoblasts. TNF-alpha and IL-1beta increased the acetyl-coenzyme A:lyso-PAF acetyltransferase activity in osteoclasts. Osteoclasts, but not osteoblasts, expressed the functional PAF receptor. PAF receptor stimulation prolonged the survival of osteoclasts in vitro. Furthermore, osteoclasts treated with a PAF receptor antagonist, and also those from PAF receptor-deficient mice, showed reductions in survival rate and Ca resorption activity. Consistently, in organ cultures, bone resorption was significantly suppressed by a PAF receptor antagonist treatment or genetic PAF receptor deficiency. Thus, these results suggest that, through the inflammatory cytokines, estrogen depletion enhances PAF production as a unique autocrine factor for osteoclast functions. Inhibition of PAF function might pave the way for a new strategy to prevent postmenopausal bone loss without disturbing osteoblast functions. |
| 巻・号 | 114(1) |
| ページ | 85-93 |
| 公開日 | 2004-7-1 |
| DOI | 10.1172/JCI20504 |
| PMID | 15232615 |
| PMC | PMC437965 |
| MeSH | Animals Bone Resorption / prevention & control Disease Models, Animal Female Mice Mice, Knockout Osteoporosis / etiology Osteoporosis / prevention & control* Ovariectomy / adverse effects* Platelet Membrane Glycoproteins / deficiency* Platelet Membrane Glycoproteins / genetics Platelet Membrane Glycoproteins / physiology* Receptors, G-Protein-Coupled / deficiency* Receptors, G-Protein-Coupled / genetics Receptors, G-Protein-Coupled / physiology* |
| IF | 11.864 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | Patent(IFI CLAIMS) |
| 各媒体での言及数の合計 | 2 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ヒト・動物細胞 | MC3T3-E1(RCB1126) |