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Updated: Jun 9, 2025

Modeling Paracrine Noncanonical Wnt Signaling In Vitro
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Modeling Paracrine Noncanonical Wnt Signaling In Vitro

Published on: December 10, 2021

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Ror2 signaling regulated by differential Wnt proteins determines pathological fate of muscle mesenchymal progenitors

Koki Kamizaki1, Mitsuko Katsukawa1, Ayano Yamamoto1

  • 1Division of Cell Physiology, Department of Physiology and Cell Biology, Graduate School of Medicine, Kobe University, Kobe, Japan.

Cell Death & Disease
|October 29, 2024
PubMed

Insights

Ror2 signaling in muscle stem cells dictates their fate. Differential Wnt ligands control Ror2, impacting muscle regeneration and pathological fat accumulation in diseases like sarcopenia.

Area of Science:

  • Muscle stem cell biology
  • Signaling pathways
  • Regenerative medicine

Background:

  • Skeletal muscle mesenchymal progenitors (MPs) are crucial for muscle repair but can contribute to fat accumulation in diseases like sarcopenia.
  • The mechanisms governing MP fate in both healthy and pathological conditions are not fully understood.

Purpose of the Study:

  • To investigate the role of Ror2, a non-canonical Wnt receptor, in regulating skeletal muscle mesenchymal progenitor (MP) fate.
  • To identify specific Wnt ligands that interact with Ror2 and influence MP behavior.

Main Methods:

  • In vitro studies using mesenchymal progenitors (MPs).
  • Analysis of Ror2 expression and its interaction with Wnt11 and Wnt5b.
  • Assessment of MP senescence and proliferation in response to Wnt ligands.

Main Results:

  • Ror2 is selectively expressed in MPs and mediates pathological features.
  • Wnt11 inhibits MP senescence, supporting normal regeneration.
  • Wnt5b promotes MP proliferation.
  • Wnt11 and Wnt5b synergistically stimulate Ror2 in degenerating muscle, causing excessive MP proliferation and fat accumulation.

Conclusions:

  • Ror2-mediated signaling, driven by differential Wnt ligands, is critical for determining the pathological fate of MPs.
  • Targeting Ror2-Wnt interactions may offer therapeutic strategies for muscle diseases characterized by fat accumulation.

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