Conversion of mechanical force into TGF-β-mediated biochemical signals

Toru Maeda, Tomoya Sakabe, Ataru Sunaga, Keiko Sakai, Alexander L. Rivera, Douglas R. Keene, Takako Sasaki, Edward Stavnezer, Joseph Iannotti, Ronen Schweitzer, Dusko Ilic, Harihara Baskaran, Takao Sakai

Research output: Contribution to journalArticlepeer-review

240 Citations (Scopus)

Abstract

Mechanical forces influence homeostasis in virtually every tissue [1, 2]. Tendon, constantly exposed to variable mechanical force, is an excellent model in which to study the conversion of mechanical stimuli into a biochemical response [3-5]. Here we show in a mouse model of acute tendon injury and in vitro that physical forces regulate the release of active transforming growth factor (TGF)-β from the extracellular matrix (ECM). The quantity of active TGF-β detected in tissue exposed to various levels of tensile loading correlates directly with the extent of physical forces. At physiological levels, mechanical forces maintain, through TGF-β/Smad2/3-mediated signaling, the expression of Scleraxis (Scx), a transcription factor specific for tenocytes and their progenitors. The gradual and temporary loss of tensile loading causes reversible loss of Scx expression, whereas sudden interruption, such as in transection tendon injury, destabilizes the structural organization of the ECM and leads to excessive release of active TGF-β and massive tenocyte death, which can be prevented by the TGF-β type I receptor inhibitor SD208. Our findings demonstrate a critical role for mechanical force in adult tendon homeostasis. Furthermore, this mechanism could translate physical force into biochemical signals in a much broader variety of tissues or systems in the body.

Original languageEnglish
Pages (from-to)933-941
Number of pages9
JournalCurrent Biology
Volume21
Issue number11
DOIs
Publication statusPublished - 07-06-2011
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

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