mTORC1 Signaling is a Critical Regulator of Postnatal Tendon Development

Sci Rep. 2017 Dec 7;7(1):17175. doi: 10.1038/s41598-017-17384-0.


Tendons transmit contractile forces between musculoskeletal tissues. Whereas the biomechanical properties of tendons have been studied extensively, the molecular mechanisms regulating postnatal tendon development are not well understood. Here we examine the role of mTORC1 signaling in postnatal tendon development using mouse genetic approaches. Loss of mTORC1 signaling by removal of Raptor in tendons caused severe tendon defects postnatally, including decreased tendon thickness, indicating that mTORC1 is necessary for postnatal tendon development. By contrast, activation of mTORC1 signaling in tendons increased tendon cell numbers and proliferation. In addition, Tsc1 conditional knockout mice presented severely disorganized collagen fibers and neovascularization in the tendon midsubstance. Interestingly, collagen fibril diameter was significantly reduced in both Raptor and Tsc1 conditional knockout mice, albeit with variations in severity. We performed RNA-seq analysis using Achilles tendons to investigate the molecular changes underlying these tendon phenotypes. Raptor conditional knockout mice showed decreased extracellular matrix (ECM) structure-related gene expression, whereas Tsc1 conditional knockout mice exhibited changes in genes regulating TGF-β/BMP/FGF signaling, as well as in genes controlling ECM structure and disassembly. Collectively, our studies suggest that maintaining physiological levels of mTORC1 signaling is essential for postnatal tendon development and maturation.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Animals, Newborn
  • Collagen / metabolism
  • Extracellular Matrix / metabolism
  • Gene Expression Profiling
  • Male
  • Mechanistic Target of Rapamycin Complex 1 / genetics
  • Mechanistic Target of Rapamycin Complex 1 / metabolism*
  • Mice
  • Mice, Knockout
  • Regulatory-Associated Protein of mTOR / physiology*
  • Signal Transduction
  • Tendons / metabolism
  • Tendons / pathology*
  • Tuberous Sclerosis Complex 1 Protein / physiology*


  • Regulatory-Associated Protein of mTOR
  • Rptor protein, mouse
  • Tsc1 protein, mouse
  • Tuberous Sclerosis Complex 1 Protein
  • Collagen
  • Mechanistic Target of Rapamycin Complex 1