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Background <p>In recent years, skeletal muscle has been recognized not only as a locomotor organ but also as a secretory organ. The bioactive molecules it releases, known as myokines, act on distant organs through the circulation and locally on muscle tissue. Previously, we identified R-spondin 3 (Rspo3) as a Type I fiber-specific myokine that promotes myoblast differentiation into Type I fibers in vitro. In this study, we further investigated whether Rspo3 is involved in regulating Type I fiber determination in vivo.</p> Methods and results <p>We generated tamoxifen-induced muscle-specific Rspo3-deficient mice and found that Rspo3 deficiency impaired Type I fiber determination during muscle regeneration. In contrast, transient overexpression of Rspo3 through in vivo electroporation enhanced the regeneration of Type I fibers, supporting its functional role in fiber-type specification.</p> Conclusion <p>This work reveals that Rspo3 as a Type I fiber specific myokine promotes Type I fiber determination during muscle regeneration in vivo.</p>

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R-spondin 3 is a myokine that mediates type I fiber determination during skeletal muscle regeneration

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年10月9日

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  • Teng Hu,
  • Yoshitaka Mita,
  • Xinhe Zhu,
  • Yasuro Furuichi,
  • Yoshimi Nakagawa,
  • Yasuko Manabe,
  • Nobuharu L. Fujii

摘要

Background

In recent years, skeletal muscle has been recognized not only as a locomotor organ but also as a secretory organ. The bioactive molecules it releases, known as myokines, act on distant organs through the circulation and locally on muscle tissue. Previously, we identified R-spondin 3 (Rspo3) as a Type I fiber-specific myokine that promotes myoblast differentiation into Type I fibers in vitro. In this study, we further investigated whether Rspo3 is involved in regulating Type I fiber determination in vivo.

Methods and results

We generated tamoxifen-induced muscle-specific Rspo3-deficient mice and found that Rspo3 deficiency impaired Type I fiber determination during muscle regeneration. In contrast, transient overexpression of Rspo3 through in vivo electroporation enhanced the regeneration of Type I fibers, supporting its functional role in fiber-type specification.

Conclusion

This work reveals that Rspo3 as a Type I fiber specific myokine promotes Type I fiber determination during muscle regeneration in vivo.