Transcription factor scleraxis vitally contributes to progenitor lineage direction in wound healing of adult tendon in mice

Tomoya Sakabe, Keiko Sakai, Toru Maeda, Ataru Sunaga, Nao Furuta, Ronen Schweitzer, Takako Sasaki, Takao Sakai

研究成果: ジャーナルへの寄稿学術論文査読

55 被引用数 (Scopus)


Tendon is a dense connective tissue that transmits high mechanical forces from skeletal muscle to bone. The transcription factor scleraxis (Scx) is a highly specific marker of both precursor and mature tendon cells (tenocytes). Mice lacking scx exhibit a specific and virtually complete loss of tendons during development. However, the functional contribution of Scx to wound healing in adult tendon has not yet been fully characterized. Here, using ScxGFP-tracking and loss-of-function systems, we show in an adult mouse model of Achilles tendon injury that paratenon cells, representing a stem cell antigen-1 (Sca-1)-positive and Scx-negative progenitor subpopulation, display Scx induction, migrate to the wound site, and produce extracellular matrix (ECM) to bridge the defect, whereas resident tenocytes exhibit a delayed response. Scx induction in the progenitors is initiated by transforming growth factor (TGF-) signaling. scx-deficient mice had migration of Sca-1-positive progenitor cell to the lesion site but impaired ECM assembly to bridge the defect. Mechanistically, scx-null progenitors displayed higher chondrogenic potential with up-regulation of SRY-box 9 (Sox9) coactivator PPAR- coactivator-1 (PGC-1) in vitro, and knock-in analysis revealed that forced expression of full-length scx significantly inhibited Sox9 expression. Accordingly, scx-null wounds formed cartilage-like tissues that developed ectopic ossification. Our findings indicate a critical role of Scx in a progenitor-cell lineage in wound healing of adult mouse tendon. These progenitor cells could represent targets in strategies to facilitate tendon repair. We propose that this lineage-regulatory mechanism in tissue progenitors could apply to a broader set of tissues or biological systems in the body.

ジャーナルJournal of Biological Chemistry
出版ステータス出版済み - 20-04-2018

All Science Journal Classification (ASJC) codes

  • 生化学
  • 分子生物学
  • 細胞生物学


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