Regulatory Mechanism of Human Connective Tissue Growth Factor (CTGF/Hcs24) Gene Expression in a Human Chondrocytic Cell Line, HCS-2/8.
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概要
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CTGF/Hcs24 is a multi-functional growth factor that potentiates either the growth or differentiation of mesenchymal cells, according to the biological conditions. Among various functional aspects of CTGF/Hcs24, it is especially notable that CTGF/Hcs24 may promote endochondral ossification in growth cartilage through all stages, and it is highly expressed in a human chondrosarcoma-derived chondrocytic cell line (HCS-2/8). In this study, to clarify the regulatory mechanism of CTGF/Hcs24 gene expression in chondrocytes, we analyzed the transcriptional activity of the CTGF/Hcs24 promoter and the effect of the CTGF/Hcs24 3'-untranslated region (3'-UTR) on gene expression in HCS-2/8 by means of an established DNA transfection and luciferase reporter gene assay system. As a result, the luciferase activity of the CTGF/Hcs24 promoter was found to be remarkably high in HCS-2/8. The 3'-ITTR of the CTGF/Hcs24 gene strongly repressed the luciferase activity in HCS-2/8, when it was linked to the downstream of the luciferase reporter gene, suggesting its functionality also in chondrocytic cells. Deletion analysis of the CTGF/Hcs24 promoter clarified a major segment responsible for the enhanced CTGF/Hcs24 promoter activity in HCS-2/8. The TGF-β response element in the DNA segment was active in HCS-2/8, and point mutations in the element moderately decreased the highly maintained promoter activity with total loss of TGF-β responsiveness. These results indicate that the strong expression of the CTGF/Hcs24 gene in HCS-2/8 was mainly caused by high transcriptional activity of the CTGF/Hcs24 promoter, and that the TGF-β response element is one of the critical elements that support the high transcription activity.
- 社団法人 日本生化学会の論文
著者
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Eguchi Takanori
Department Of Biochemistiy And Molecular Dentistry Okayama University Graduate School Of Medicine An
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NAKANISHI Tohru
Department of Biochemistiy and Molecular Dentistry, Okayama University Graduate School of Medicine a
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TAKIGAWA Masaharu
Department of Biochemistiy and Molecular Dentistry, Okayama University Graduate School of Medicine a
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Hattori Takako
Department Of Biochemistiy And Molecular Dentistry Okayama University Graduate School Of Medicine An
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Kuboki Takuo
Department Of Fixed Prosthodontics Okayama University Dental School
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Shimo Tsuyoshi
Department Of Biochemistiy And Molecular Dentistry Okayama University Graduate School Of Medicine An
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Yatani Hirofumi
Department Of Fixed Prosthodontics
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Kondo Seiji
Department Of Biochemistiy And Molecular Dentistry Okayama University Graduate School Of Medicine An
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Kubota Satoshi
Department Of Agriculture Kochi University
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