論文 - 詳細
| RRC ID | 54106 |
|---|---|
| 著者 | Tsukune N, Naito M, Ohashi A, Ninomiya T, Sato S, Takahashi T. |
| タイトル | Forced expression of mouse progerin attenuates the osteoblast differentiation interrupting β-catenin signal pathway in vitro. |
| ジャーナル | Cell Tissue Res |
| Abstract |
Nuclear protein, lamin A, which is a component of inner membrane on nucleoplasm, plays a role in nuclear formation and cell differentiation. The expression of mutated lamin A, termed progerin, causes a rare genetic aging disorder, Hutchinson-Gilford progeria syndrome, which shows abnormal bone formation with the decrease in a number of osteoblasts and osteocytes. However, exact molecular mechanism how progerin exerts depressive effects on osteogenesis has not been fully understood. Here, we created mouse lamin A dC50 cDNA encoding progerin that lacks 50 amino acid residues at C-terminus, transfected it in mouse preosteoblast-like MC3T3-E1 cells, and examined the changes in osteoblast phenotype. When lamin A dC50-expressed cells were cultured with differentiation-inductive medium, alkaline phosphatase (ALP) activity and mRNA levels of major osteoblast markers, type I collagen (Col1), bone sialoprotein (BSP), dentine matrix protein 1 (DMP1), and Runx2 were significantly decreased, and no mineralized nodules were detected as seen in control cells expressing empty vector. In the culture with mineralization-inductive medium, mRNA levels of BSP, osteocalcin, DMP1, Runx2, and osterix were strongly decreased parallel with loss of mineralization in lamin A dC50-expressed cells, while mineralized nodules appear at 21 days in control cells. Furthermore, lamin A dC50 expression was depressed nuclear localization of β-catenin with the decrease of GSK-3β phosphorylation level. These results suggest that lamin A dC50 depresses osteoblast differentiation in both early and late stages, and it negatively regulates β-catenin activity interacting with GSK-3β in cytoplasm. |
| 巻・号 | 375(3) |
| ページ | 655-664 |
| 公開日 | 2019-3-1 |
| DOI | 10.1007/s00441-018-2930-y |
| PII | 10.1007/s00441-018-2930-y |
| PMID | 30284086 |
| MeSH | Alkaline Phosphatase / metabolism Amino Acid Sequence Animals Calcification, Physiologic / drug effects Cell Differentiation* / drug effects Cell Line Cell Nucleus / drug effects Cell Nucleus / metabolism Collagen Type I / metabolism Deoxycholic Acid / pharmacology Humans Indoles / pharmacology Lamin Type A / chemistry Lamin Type A / metabolism* Maleimides / pharmacology Mice Osteoblasts / cytology* Osteoblasts / drug effects Osteoblasts / metabolism* Signal Transduction* / drug effects beta Catenin / metabolism* |
| IF | 4.044 |
| 引用数 | 0 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
|
| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 1 |
| 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) |