Scleraxis is a transcriptional activator that regulates the expression of Tenomodulin, a marker of mature tenocytes and ligamentocytes

• 宿南, 知佐

  Department of Molecular Biology and Biochemistry, Division of Dental Sciences, Graduate School of Biomedical and Health Sciences, Hiroshima University

• 滝本, 晶

  Laboratory of Cellular Differentiation, Institute for Frontier Life and Medical Sciences, Kyoto University

• 西崎, 有利子

  Laboratory of Cellular Differentiation, Institute for Frontier Life and Medical Sciences, Kyoto University・Functional Morphology Laboratory, Department of Clinical Pharmacy, Faculty of Pharmacy, Yokohama University of Pharmacy

• 三浦, 重徳

  Department of Molecular Biology and Biochemistry, Division of Dental Sciences, Graduate School of Biomedical and Health Sciences, Hiroshima University

• 渡邊, 仁美

  Department of Molecular Biology and Biochemistry, Division of Dental Sciences, Graduate School of Biomedical and Health Sciences, Hiroshima University

• 近藤, 玄

  Laboratory of Cellular Differentiation, Institute for Frontier Life and Medical Sciences, Kyoto University

• 開, 祐司

  Laboratory of Integrative Biological Science, Institute for Frontier Life and Medical Sciences, Kyoto University

• Sakuma, Tetsushi

  Department of Mathematical and Life Sciences, Graduate School of Science, Hiroshima University

• Yamamoto, Takashi

  Department of Mathematical and Life Sciences, Graduate School of Science, Hiroshima University

• Kondoh, Gen

  Laboratory of Integrative Biological Science, Institute for Frontier Life and Medical Sciences, Kyoto University

• Hiraki, Yuji

  Laboratory of Cellular Differentiation, Institute for Frontier Life and Medical Sciences, Kyoto University

抄録

Tenomodulin (Tnmd) is a type II transmembrane glycoprotein predominantly expressed in tendons and ligaments. We found that scleraxis (Scx), a member of the Twist-family of basic helix-loop-helix transcription factors, is a transcriptional activator of Tnmd expression in tenocytes. During embryonic development, Scx expression preceded that of Tnmd. Tnmd expression was nearly absent in tendons and ligaments of Scx-deficient mice generated by transcription activator-like effector nucleases-mediated gene disruption. Tnmd mRNA levels were dramatically decreased during serial passages of rat tenocytes. Scx silencing by small interfering RNA significantly suppressed endogenous Tnmd mRNA levels in tenocytes. Mouse Tnmd contains five E-box sites in the ~1-kb 5′-flanking region. A 174-base pair genomic fragment containing a TATA box drives transcription in tenocytes. Enhancer activity was increased in the upstream region (−1030 to −295) of Tnmd in tenocytes, but not in NIH3T3 and C3H10T1/2 cells. Preferential binding of both Scx and Twist1 as a heterodimer with E12 or E47 to CAGATG or CATCTG and transactivation of the 5′-flanking region were confirmed by electrophoresis mobility shift and dual luciferase assays, respectively. Scx directly transactivates Tnmd via these E-boxes to positively regulate tenocyte differentiation and maturation.

収録刊行物

• Scientific Reports

  Scientific Reports 8 3155-, 2018-02-16

  Springer Nature

キーワード

• Multidisciplinary

詳細情報

• CRID: 1050564288161118208
• NII論文ID: 120006522882
• ISSN: 20452322
• DOI: 10.1038/s41598-018-21194-3
• HANDLE: 2433/234567
• Web Site: https://www.nature.com/articles/s41598-018-21194-3
• Web Site: https://www.nature.com/articles/s41598-018-21194-3.pdf
• 本文言語コード: en
• 資料種別: journal article
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