論文 - 詳細
| RRC ID | 18682 |
|---|---|
| 著者 | Noguchi K, Watanabe Y, Fuse T, Takizawa M. |
| タイトル | A new chondrogenic differentiation initiator with the ability to up-regulate SOX trio expression. |
| ジャーナル | J Pharmacol Sci |
| Abstract |
During random screening for chondrogenic differentiation inducers, we found that Compound-1, 4-[4-(2,3-dihydro-1,4-benzodioxin-6-yl)-1H-pyrazol-3-yl]benzene-1,3-diol, initiated chondrogenic differentiation of the chondroprogenitor cell line ATDC5. Compound-1 initiated chondrogenic differentiation of the mesenchymal stem cell line C3H10T1/2 in regions where cell aggregates formed and simultaneously inhibited adipogenic differentiation. In C3H10T1/2 cells, Compound-1 increased the expression of Sry-related high-mobility-group box transcription factors L-SOX5, SOX6, and SOX9 (SOX trio) more strongly than bone morphogenic protein (BMP)-2. cAMP-dependent protein kinase (PKA) inhibitors suppressed Compound-1-dependent L-SOX5 and SOX6 up-regulation. PKA inhibitors also suppressed the up-regulation of aggrecan mRNA induced by Compound-1, indicating that increases in L-SOX5 and SOX6 mRNA, in which the PKA pathway participates, are involved in the mechanisms behind the action of Compound-1. On the other hand, the SOX6 and aggrecan gene expression, which were up-regulated by BMP-2, were not affected by the PKA inhibitor. Compound-1 induced chondrogenic differentiation of bone marrow stromal cells and recovered cartilage matrix production by primary chondrocytes, which had been decreased by interleukin-1beta. These results show the potential of Compound-1 to be a new cartilage repair agent for inducing chondrogenic differentiation via SOX trio up-regulation. |
| 巻・号 | 112(1) |
| ページ | 89-97 |
| 公開日 | 2010-1-1 |
| DOI | 10.1254/jphs.09254fp |
| PII | JST.JSTAGE/jphs/09254FP |
| PMID | 20051655 |
| MeSH | Animals Bridged Bicyclo Compounds, Heterocyclic / chemistry* Bridged Bicyclo Compounds, Heterocyclic / pharmacology* Cell Differentiation / drug effects Cell Line, Tumor Chondrocytes / drug effects* Chondrocytes / metabolism Chondrogenesis / drug effects* Clone Cells Gene Expression Regulation / drug effects Humans Male Mesenchymal Stem Cells / drug effects* Mesenchymal Stem Cells / metabolism Mice Mice, Inbred C3H Pyrazoles / chemistry* Pyrazoles / pharmacology* Rabbits Rats Rats, Sprague-Dawley SOX9 Transcription Factor / biosynthesis* SOXD Transcription Factors / biosynthesis* Up-Regulation / drug effects* Up-Regulation / physiology |
| IF | 2.835 |
| 引用数 | 5 |
| WOS 分野 | PHARMACOLOGY & PHARMACY |
| 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 | ATDC5(RCB0565) |