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Updated: Aug 27, 2025

Author Spotlight: Advancements in Cell and Tissue Engineering for Tendon Repair
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The INSR/AKT/mTOR pathway regulates the pace of myogenesis in a syndecan-3-dependent manner

Fiona K Jones1, Alexander M Phillips2, Andrew R Jones3

  • 1Department of Biochemistry and Cell Biology, Stony Brook University, Stony Brook, NY, USA.

Matrix Biology : Journal of the International Society for Matrix Biology
|September 24, 2022
PubMed

Insights

Syndecan-3 (SDC3) restrains muscle stem cell (MuSC) proliferation and prevents premature differentiation by inhibiting insulin receptor signaling. Downregulating SDC3 or blocking the AKT pathway restores normal muscle regeneration.

Area of Science:

  • Muscle stem cell biology
  • Cell signaling pathways
  • Regenerative medicine

Background:

  • Muscle stem cells (MuSCs) are crucial for muscle repair and regeneration.
  • Extracellular signals and coreceptors like syndecan-3 (SDC3) regulate MuSC fate.
  • Understanding SDC3's role is key to controlling myogenesis.

Purpose of the Study:

  • To comprehensively map SDC3-mediated signaling in muscle stem cells.
  • To elucidate the mechanism by which SDC3 regulates myogenesis.
  • To identify SDC3's function in controlling the timing of differentiation.

Main Methods:

  • Phosphoproteomics to identify SDC3-regulated phosphosites.
  • Investigating the insulin receptor (INSR)/AKT/mTOR pathway.
  • Genetic manipulation (knockdown) and pharmacological inhibition.

Main Results:

  • SDC3 globally regulates signal transduction in MuSCs, particularly the INSR/AKT/mTOR pathway.
  • SDC3 directly interacts with INSR, inhibiting downstream signaling.
  • Restoring INSR signaling or inhibiting AKT rescues differentiation in Sdc3-deficient MuSCs.

Conclusions:

  • SDC3 acts as a timekeeper, preventing premature differentiation of proliferating MuSCs.
  • SDC3 inhibits myogenesis by suppressing insulin receptor signaling.
  • SDC3 downregulation is a critical event initiating differentiation.
Keywords:
AKTDifferentiationInsulin receptorInsulin signalingMuscle stem cellsMyogenesisPhosphoproteomicsProliferationProteoglycanProteomicsSatellite cellsSyndecan-3SyndecansmTOR

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