論文 - 詳細
| RRC ID | 1255 |
|---|---|
| 著者 | Mogi M, Togari A. |
| タイトル | Activation of caspases is required for osteoblastic differentiation. |
| ジャーナル | J Biol Chem |
| Abstract |
Previous studies have shown that mouse osteoblastic MC3T3-E1 cells undergo apoptosis when exposed to a mixture of proinflammatory cytokines. Bone morphogenetic protein (BMP)s are important regulators of osteoblast differentiation. Because regulation of osteoblastic differentiation is poorly understood, we sought to determine if BMP-4-induced differentiation of osteoblastic cells depends on the activity of the key apoptotic proteases, i.e. the caspases. BMP-4 induced the growth arrest and differentiation of osteoblastic cell line MC3T3-E1, as evidenced by the appearance of osteoblastic phenotypes such as alkaline phosphatase (ALP) activation and parathyroid hormone (PTH)-dependent production of cAMP. Surprisingly, BMP-4 induced transient and potent activation of caspase-8, caspase-2, and caspase-3, in this order. However, no apoptosis or necrosis in BMP-4-treated cells could be detected by FACS using annexin-V/propodium iodine double staining. Peptide inhibition of caspase activity led to a dramatic reduction in ALP activation and PTH-induced production of cAMP in BMP-4-treated cells. Although BMP-4 treatment resulted in cell-cycle G0/G1 arrest as detected by FACS cell-cycle analysis, caspase inhibitors (caspase-8, caspase-2, and caspase-3 inhibitors) could block the G0/G1 arrest in MC3T3-E1 cells. Taken together, these results confirm a unique and unanticipated role for the caspase-mediated signal cascade in the differentiation of osteoblasts. |
| 巻・号 | 278(48) |
| ページ | 47477-82 |
| 公開日 | 2003-11-28 |
| DOI | 10.1074/jbc.M307055200 |
| PII | S0021-9258(20)75770-4 |
| PMID | 12954609 |
| MeSH | Alkaline Phosphatase / metabolism Animals Apoptosis Blotting, Western Bone Morphogenetic Protein 4 Bone Morphogenetic Proteins / metabolism Caspase 2 Caspase 3 Caspase 8 Caspase 9 Caspases / metabolism* Cell Cycle Cell Differentiation Cell Division Cell Line Cell Separation Cyclic AMP / metabolism Enzyme Activation Enzyme-Linked Immunosorbent Assay Flow Cytometry Mice Osteoblasts / cytology* Parathyroid Hormone / metabolism Phenotype Time Factors |
| IF | 4.238 |
| 引用数 | 104 |
| WOS 分野 | BIOCHEMISTRY & MOLECULAR 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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| 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) |