Mechanical force regulates tendon extracellular matrix organization and tenocyte morphogenesis through TGFbeta signaling
- University of California, Irvine, United States
- Massachusetts General Hospital, United States
Abstract
Mechanical forces between cells and extracellular matrix (ECM) influence cell shape and function. Tendons are ECM-rich tissues connecting muscles with bones that bear extreme tensional force. Analysis of transgenic zebrafish expressing mCherry driven by the tendon determinant scleraxis reveals that tendon fibroblasts (tenocytes) extend arrays of microtubule-rich projections at the onset of muscle contraction. In the trunk, these form a dense curtain along the myotendinous junctions at somite boundaries, perpendicular to myofibers, suggesting a role as force sensors to control ECM production and tendon strength. Paralysis or destabilization of microtubules reduces projection length and surrounding ECM, both of which are rescued by muscle stimulation. Paralysis also reduces SMAD3 phosphorylation in tenocytes and chemical inhibition of TGFβ signaling shortens tenocyte projections. These results suggest that TGFβ, released in response to force, acts on tenocytes to alter their morphology and ECM production, revealing a feedback mechanism by which tendons adapt to tension.
Data availability
All data generated or analyzed during this study are included in the manuscript and supporting files.
Article and author information
Author details
Lauren Fallon Kanzaki
Thomas F Schilling
Funding
National Institutes of Health (R01 AR67797)
- Thomas F Schilling
National Institutes of Health (R01 DE013828)
- Thomas F Schilling
National Institutes of Health (R21 AR62792)
- Thomas F Schilling
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: This study was performed in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. All of the animals were handled according to approved institutional animal care and use committee (IACUC) protocols (#2000-2149) of the University of California, Irvine. Embryos were anesthetized with tricaine before stimulation assays.
Copyright
© 2018, Subramanian et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Mechanical force regulates tendon extracellular matrix organization and tenocyte morphogenesis through TGFbeta signaling
eLife 7:e38069.
https://doi.org/10.7554/eLife.38069
