PDGFRβ signaling restrains myocyte function to limit the regenerative capacity of skeletal muscle

Area of Science:

• Muscle biology
• Regenerative medicine
• Cell signaling

Background:

• Skeletal muscle regeneration relies on myocyte fusion to form multinucleated myotubes.
• The precise molecular regulators of this critical cell fusion process remain incompletely understood.

Purpose of the Study:

• To investigate the role of platelet-derived growth factor receptor β (PDGFRβ) signaling in skeletal muscle cell fusion and regeneration.
• To identify PDGFRβ as a potential therapeutic target for enhancing muscle repair.

Main Methods:

• Genetic manipulation of Pdgfrb in mouse models.
• Pharmacological inhibition of PDGFRβ activity.
• Analysis of myotube formation, myonuclear accretion, and myofiber size in vitro and in vivo.
• Investigated downstream signaling pathways including STAT1 and TGF-β.

Main Results:

• Genetic deletion of Pdgfrb improved muscle regeneration and increased myofiber size.
• PDGFRβ activation impaired muscle repair and stalled myotube development by limiting cell fusion.
• Inhibition of PDGFRβ promoted myonuclear accretion in both mouse and human myotubes.
• PDGFRβ signaling cooperates with TGF-β and requires STAT1 activation; blocking STAT1 phosphorylation enhanced regeneration.

Conclusions:

• PDGFRβ signaling acts as a critical checkpoint regulating myocyte fusion and skeletal muscle regeneration.
• Targeting PDGFRβ activity offers a promising therapeutic strategy for improving muscle repair and treating muscle-wasting conditions.