論文 - 詳細
| RRC ID | 42618 |
|---|---|
| 著者 | Maran A, Gorny G, Oursler MJ, Zhang M, Shogren KL, Yaszemski MJ, Turner RT. |
| タイトル | 2-methoxyestradiol inhibits differentiation and is cytotoxic to osteoclasts. |
| ジャーナル | J Cell Biochem |
| Abstract |
2-Methoxyestradiol (2-ME), a naturally occurring metabolite of 17beta-estradiol, is highly cytotoxic to a wide range of tumor cells but is harmless to most normal cells. However, 2-ME prevented bone loss in ovariectomized rats, suggesting it inhibits bone resorption. These studies were performed to determine the direct effects of 2-ME on cultured osteoclasts. 2-ME (2 microM) reduced osteoclast number by more than 95% and induced apoptosis in three cultured osteoclast model systems (RAW 264.7 cells cultured with RANKL, marrow cells co-cultured with stromal support cells, and spleen cells cultured without support cells in media supplemented with RANKL and macrophage colony stimulating factor (M-CSF)). The 2-ME-mediated effect was ligand specific; 2-hydroxyestradiol (2-OHE), the immediate precursor to 2-ME, exhibited less cytotoxicity; and 2-methoxyestrone (2-MEOE1) the estrone analog of 2-ME, was not cytotoxic. Co-treatment with ICI 182,780 did not antagonize 2-ME, suggesting that the cytotoxicity was not estrogen receptor-dependent. 2-ME-induced cell death in RAW 264.7 cells coincided with an increase in gene expression of cytokines implicated in inhibition of differentiation and induction of apoptosis. In addition, the 2-ME-mediated decrease in cell survival was partially inhibited by anti-lymphotoxin(LT)beta antibodies, suggesting that 2-ME-dependent effects involve LTbeta. These results suggest that 2-ME could be useful for treating skeletal diseases in which bone resorption is increased, such as postmenopausal osteoporosis and cancer metastasis to bone. |
| 巻・号 | 99(2) |
| ページ | 425-34 |
| 公開日 | 2006-10-1 |
| DOI | 10.1002/jcb.20924 |
| PMID | 16619269 |
| MeSH | 2-Methoxyestradiol Animals Apoptosis / drug effects Bone Resorption / prevention & control Cell Differentiation / drug effects Cell Line Cell Survival / drug effects Cells, Cultured Cytokines / genetics Estradiol / analogs & derivatives* Estradiol / pharmacology Estrogen Receptor Modulators / pharmacology Female Fulvestrant Lymphotoxin-alpha / antagonists & inhibitors Lymphotoxin-beta Membrane Proteins / antagonists & inhibitors Mice Osteoclasts / cytology* Osteoclasts / drug effects* Osteoclasts / metabolism RNA, Messenger / genetics RNA, Messenger / metabolism Rats |
| IF | 4.237 |
| 引用数 | 19 |
| WOS 分野 | BIOCHEMISTRY & MOLECULAR BIOLOGY 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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| 最多言及媒体 | Patent(IFI CLAIMS) |
| 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 | ST2(RCB0224) |