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ナカシマ カズヒサ
Nakashima Kazuhisa
中島 和久 所属 鶴見大学 歯学部 歯学科 薬理学 職種 准教授 |
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| 論文種別 | 【査読あり】 研究論文（学術雑誌） |
| 言語種別 | 英語 |
| 査読の有無 | 査読あり |
| 表題 | NFAT and Osterix cooperatively regulate bone formation |
| 掲載誌名 | 正式名：NATURE MEDICINE ISSNコード：10788956 |
| 出版社 | NATURE PUBLISHING GROUP |
| 巻・号・頁 | 11(8),pp.880-885 |
| 著者・共著者 | T Koga,Y Matsui,M Asagiri,T Kodama,B de Crombrugghe,K Nakashima,H Takayanagi |
| 発行年月 | 2005/08 |
| 概要 | Immunosuppressants are crucial in the prevention of detrimental immune reactions associated with allogenic organ transplantation, but they often cause adverse effects in a number of biological systems, including the skeletal system(1,2). Calcineurin inhibitors FK506 and cyclosporin A inhibit nuclear factor of activated T cells (NFAT) activity and induce strong immunosuppression(3-5). Among NFAT proteins, NFATc1 is crucial for the differentiation of bone-resorbing osteoclasts(6,7). Here we show FK506 administration induces the reduction of bone massdespite a blockade of osteoclast differentiation. This reduction is caused by severe impairment of bone formation, suggesting that NFAT transcription factors also have an important role in the transcriptional program of osteoblasts. In fact, bone formation is inhibited in Nfatc1- and Nfatc2-deficient cells as well as in FK506-treated osteoblasts. Overexpression of NFATc1 stimulates Osterix(8)-dependent activation of the Col1a1 (encoding type I collagen) promoter, but not Runx2-dependent activation of the Bglap1 (encoding osteocalcin) promoter(9). NFAT and Osterix form a complex that binds to DNA, and this interaction is important for the |
| DOI | 10.1038/nm1270 |
| PMID | 16041384 |