論文 - 詳細
| RRC ID | 3868 |
|---|---|
| 著者 | Tsubaki M, Kato C, Manno M, Ogaki M, Satou T, Itoh T, Kusunoki T, Tanimori Y, Fujiwara K, Matsuoka H, Nishida S. |
| タイトル | Macrophage inflammatory protein-1alpha (MIP-1alpha) enhances a receptor activator of nuclear factor kappaB ligand (RANKL) expression in mouse bone marrow stromal cells and osteoblasts through MAPK and PI3K/Akt pathways. |
| ジャーナル | Mol Cell Biochem |
| Abstract |
Osteolytic lesions are rapidly progressive during the terminal stages of myeloma, and the bone pain or bone fracture that occurs at these lesions decreases the patients' quality of life to a notable degree. In relation to the etiology of this bone destruction, it has been reported recently that MIP-1alpha, produced in large amounts in myeloma patients, acts indirectly on osteoclastic precursor cells, and activates osteoclasts by way of bone-marrow stromal cells or osteoblasts, although the details of this process remain obscure. In the present study, our group investigated the mechanism by which RANKL expression is induced by MIP-1alpha and the effects of MIP-1alpha on the activation of osteoclasts. RANKL mRNA and RANKL protein expressions increased in both ST2 cells and MC3T3-E1 cells in a MIP-1alpha concentration-dependent manner. RANKL mRNA expression began to increase at 1 h after the addition of MIP-1alpha; the increase became remarkable at 2 h, and continuous expression was observed subsequently. Both ST2 and MC3T3-E1 cells showed similar levels of increased RANKL protein expression at 1, 2, and 3 days after the addition of MIP-1alpha. After the addition of MIP-1alpha, the amount of phosphorylated ERK1/2 and Akt protein expressions showed an increase, as compared to the corresponding amount in the control group. On the other hand, the amount of phosphorylated p38MAPK protein expression showed a decrease from the amount in the control group after the addition of MIP-1alpha. U0126 (a MEK1/2 inhibitor) or LY294002 (a PI3K inhibitor) was added to ST2 and MC3T3-E1 cells, and was found to inhibit RANKL mRNA and RANKL protein expression in these cells. When SB203580, a p38MAPK inhibitor, was added, RANKL mRNA and RANKL protein expression were increased in these cells. MIP-1alpha was found to promote osteoclastic differentiation of C7 cells, an osteoclastic precursor cell line, in a MIP-1alpha concentration-dependent manner. MIP-1alpha promoted differentiation into osteoclasts more extensively in C7 cells incubated together with ST2 and MC3T3-E1 cells than in C7 cells incubated alone. These results suggested that MIP-1alpha directly acts on the osteoclastic precursor cells and induces osteoclastic differentiation. This substance also indirectly induces osteoclastic differentiation through the promotion of RANKL expression in bone-marrow stromal cells and osteoblasts. The findings of this investigation suggested that activation of the MEK/ERK and the PI3K/Akt pathways and inhibition of p38MAPK pathway were involved in RANKL expression induced by MIP-1alpha in bone-marrow stromal cells and osteoblasts. This finding may be useful in the development of an osteoclastic inhibitor that targets intracellular signaling factors. |
| 巻・号 | 304(1-2) |
| ページ | 53-60 |
| 公開日 | 2007-10-1 |
| DOI | 10.1007/s11010-007-9485-7 |
| PMID | 17549607 |
| MeSH | Animals Bone Marrow Cells / drug effects* Bone Marrow Cells / metabolism Butadienes / pharmacology Cell Differentiation / drug effects Cells, Cultured Chemokine CCL3 / pharmacology* Chromones / pharmacology Enzyme Inhibitors / pharmacology Extracellular Signal-Regulated MAP Kinases / metabolism* Imidazoles / pharmacology Mice Morpholines / pharmacology Nitriles / pharmacology Oncogene Protein v-akt / metabolism* Osteoblasts / drug effects* Osteoblasts / metabolism Osteoclasts / cytology Osteoclasts / drug effects Phosphatidylinositol 3-Kinases / metabolism* Phosphorylation / drug effects Pyridines / pharmacology RANK Ligand / genetics* RANK Ligand / metabolism Signal Transduction / drug effects Stromal Cells / drug effects Stromal Cells / metabolism |
| IF | 2.795 |
| 引用数 | 52 |
| WOS 分野 | CELL BIOLOGY |
| 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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| 各媒体での言及数の合計 | 0 |
| リソース情報 | |
| ヒト・動物細胞 | ST2(RCB0224) MC3T3-E1(RCB1126) |