<i>Gtf2ird1</i>-Dependent <i>Mohawk</i> Expression Regulates Mechanosensing Properties of the Tendon
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- Tomohiro Kayama
- Department of Systems BioMedicine, Tokyo Medical and Dental University, Tokyo, Japan
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- Masaki Mori
- Department of Systems BioMedicine, Tokyo Medical and Dental University, Tokyo, Japan
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- Yoshiaki Ito
- Department of Systems BioMedicine, Tokyo Medical and Dental University, Tokyo, Japan
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- Takahide Matsushima
- Department of Systems BioMedicine, Tokyo Medical and Dental University, Tokyo, Japan
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- Ryo Nakamichi
- Department of Systems BioMedicine, Tokyo Medical and Dental University, Tokyo, Japan
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- Hidetsugu Suzuki
- Department of Systems BioMedicine, Tokyo Medical and Dental University, Tokyo, Japan
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- Shizuko Ichinose
- Research Center for Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan
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- Mitsuru Saito
- Department of Orthopaedic Surgery, The Jikei University School of Medicine, Tokyo, Japan
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- Keishi Marumo
- Department of Orthopaedic Surgery, The Jikei University School of Medicine, Tokyo, Japan
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- Hiroshi Asahara
- Department of Systems BioMedicine, Tokyo Medical and Dental University, Tokyo, Japan
書誌事項
- 公開日
- 2016-04-01
- 資源種別
- journal article
- 権利情報
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- http://creativecommons.org/licenses/by/4.0/
- DOI
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- 10.1128/mcb.00950-15
- 公開者
- Informa UK Limited
説明
Mechanoforces experienced by an organ are translated into biological information for cellular sensing and response. In mammals, the tendon connective tissue experiences and resists physical forces, with tendon-specific mesenchymal cells called tenocytes orchestrating extracellular matrix (ECM) turnover. We show that Mohawk (Mkx), a tendon-specific transcription factor, is essential in mechanoresponsive tenogenesis through regulation of its downstream ECM genes such as type I collagens and proteoglycans such as fibromodulin both in vivo and in vitro Wild-type (WT) mice demonstrated an increase in collagen fiber diameter and density in response to physical treadmill exercise, whereas in Mkx(-/-) mice, tendons failed to respond to the same mechanical stimulation. Furthermore, functional screening of the Mkx promoter region identified several upstream transcription factors that regulate Mkx In particular, general transcription factor II-I repeat domain-containing protein 1 (Gtf2ird1) that is expressed in the cytoplasm of unstressed tenocytes translocated into the nucleus upon mechanical stretching to activate the Mkx promoter through chromatin regulation. Here, we demonstrate that Gtf2ird1 is essential for Mkx transcription, while also linking mechanical forces to Mkx-mediated tendon homeostasis and regeneration.
収録刊行物
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- Molecular and Cellular Biology
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Molecular and Cellular Biology 36 (8), 1297-1309, 2016-04-01
Informa UK Limited
