@article{be56a35076c24ee28648dbb7878d54c0,
title = "In vitro Neo-Genesis of Tendon/Ligament-Like Tissue by Combination of Mohawk and a Three-Dimensional Cyclic Mechanical Stretch Culture System",
abstract = "Tendons and ligaments are pivotal connective tissues that tightly connect muscle and bone. In this study, we developed a novel approach to generate tendon/ligament-like tissues with a hierarchical structure, by introducing the tendon/ligament-specific transcription factor Mohawk (MKX) into the mesenchymal stem cell (MSC) line C3H10T1/2 cells, and by applying an improved three-dimensional (3D) cyclic mechanical stretch culture system. In our developed protocol, a combination of stable Mkx expression and cyclic mechanical stretch synergistically affects the structural tendon/ligament-like tissue generation and tendon related gene expression. In a histological analysis of these tendon/ligament-like tissues, an organized extracellular matrix (ECM), containing collagen type III and elastin, was observed. Moreover, we confirmed that Mkx expression and cyclic mechanical stretch, induced the alignment of structural collagen fibril bundles that were deposited in a fibripositor-like manner during the generation of our tendon/ligament-like tissues. Our findings provide new insights for the tendon/ligament biomaterial fields.",
keywords = "Mohawk, ligament, mechanical-stress, tendon, tissue engineering",
author = "Kensuke Kataoka and Ryota Kurimoto and Hiroki Tsutsumi and Tomoki Chiba and Tomomi Kato and Kana Shishido and Mariko Kato and Yoshiaki Ito and Yuichiro Cho and Osamu Hoshi and Ayako Mimata and Yuriko Sakamaki and Ryo Nakamichi and Lotz, {Martin K.} and Keiji Naruse and Hiroshi Asahara",
note = "Funding Information: We thank Dr. Naoko Nakamura, Dr. Tsuyoshi Kimura, and Prof. Akio Kishida from the Department of Material-Based Medical Engineering, Tokyo Medical and Dental University, Tokyo, Japan for their critical discussions. We also thank all the members of the Department of Systems BioMedicine in Tokyo Medical and Dental University for their support. We would like to thank Editage (www.editage.jp) for the English language editing. Funding. This work was supported by JSPS KAKENHI (Grant Nos.: 26113008, 15H02560, 15K15544, 18K196013, and 19KK0227 to HA, 26220203 to KN, and 18J13487 to KK), Core Research for the Evolutionary Science and Technology (CREST) funding from the Japan Science and Technology Agency and AMED-CREST (Grant Nos.: JP15gm0410001 and JP19gm0810008 to HA), and grants from the NIH (Grant Nos.: AR050631 and AR065379 to HA). KN was supported by the Menicon Co., Ltd., Aichi, Japan. Publisher Copyright: {\textcopyright} Copyright {\textcopyright} 2020 Kataoka, Kurimoto, Tsutsumi, Chiba, Kato, Shishido, Kato, Ito, Cho, Hoshi, Mimata, Sakamaki, Nakamichi, Lotz, Naruse and Asahara.",
year = "2020",
month = jun,
day = "2",
doi = "10.3389/fcell.2020.00307",
language = "English",
volume = "8",
journal = "Frontiers in Cell and Developmental Biology",
issn = "2296-634X",
publisher = "Frontiers Media S. A.",
}