論文 - 詳細
| RRC ID | 1928 |
|---|---|
| 著者 | Ikeda T, Kamekura S, Mabuchi A, Kou I, Seki S, Takato T, Nakamura K, Kawaguchi H, Ikegawa S, Chung UI. |
| タイトル | The combination of SOX5, SOX6, and SOX9 (the SOX trio) provides signals sufficient for induction of permanent cartilage. |
| ジャーナル | Arthritis Rheum |
| Abstract |
OBJECTIVE:To regenerate permanent cartilage, it is crucial to know not only the necessary conditions for chondrogenesis, but also the sufficient conditions. The objective of this study was to determine the signal sufficient for chondrogenesis. METHODS:Embryonic stem cells that had been engineered to fluoresce upon chondrocyte differentiation were treated with combinations of factors necessary for chondrogenesis, and chondrocyte differentiation was detected as fluorescence. We screened for the combination that could induce fluorescence within 3 days. Then, primary mesenchymal stem cells, nonchondrogenic immortalized cell lines, and primary dermal fibroblasts were treated with the combination, and the induction of chondrocyte differentiation was assessed by detecting the expression of the cartilage marker genes and the accumulation of proteoglycan-rich matrix. The effects of monolayer, spheroid, and 3-dimensional culture systems on induction by combinations of transcription factors were compared. The effects of the combination on hypertrophic and osteoblastic differentiation were evaluated by detecting the expression of the characteristic marker genes. RESULTS:No single factor induced fluorescence. Among various combinations examined, only the SOX5, SOX6, and SOX9 combination (the SOX trio) induced fluorescence within 3 days. The SOX trio successfully induced chondrocyte differentiation in all cell types tested, including nonchondrogenic types, and the induction occurred regardless of the culture system used. Contrary to the conventional chondrogenic techniques, the SOX trio suppressed hypertrophic and osteogenic differentiation at the same time. CONCLUSION:These data strongly suggest that the SOX trio provides signals sufficient for the induction of permanent cartilage. |
| 巻・号 | 50(11) |
| ページ | 3561-73 |
| 公開日 | 2004-11-1 |
| DOI | 10.1002/art.20611 |
| PMID | 15529345 |
| MeSH | Adult Animals Biomarkers / metabolism Cartilage / embryology* Cartilage / growth & development Cell Line, Transformed Cells, Cultured Chondrocytes / physiology DNA-Binding Proteins / biosynthesis DNA-Binding Proteins / metabolism* DNA-Binding Proteins / pharmacology Embryo, Mammalian / cytology Embryo, Mammalian / metabolism Embryo, Mammalian / physiology Embryonic Development / physiology Fibroblasts / metabolism Fibroblasts / physiology Gene Expression Regulation / physiology High Mobility Group Proteins / biosynthesis High Mobility Group Proteins / metabolism* High Mobility Group Proteins / pharmacology High Mobility Group Proteins / physiology Humans Mice Mice, Inbred C57BL Nuclear Proteins / biosynthesis Nuclear Proteins / metabolism* Nuclear Proteins / pharmacology Phenotype SOX9 Transcription Factor SOXD Transcription Factors Signal Transduction / physiology* Skin / cytology Stem Cells / metabolism* Subcutaneous Tissue / drug effects Subcutaneous Tissue / growth & development Transcription Factors / biosynthesis Transcription Factors / metabolism* Transcription Factors / pharmacology Transcription Factors / physiology |
| 引用数 | 241 |
| WOS 分野 | RHEUMATOLOGY |
| リソース情報 | |
| ヒト・動物細胞 | HuH-7(RCB1366) |