Loss of CRY2 promotes regenerative myogenesis by enhancing PAX7 expression and satellite cell proliferation

Area of Science:

• Muscle biology
• Circadian rhythms
• Regenerative medicine

Background:

• Skeletal muscle regeneration relies on satellite cells.
• The circadian clock, including Cryptochrome 2 (CRY2), influences satellite cell function.
• CRY2's role in muscle repair is debated.

Purpose of the Study:

• To investigate the function of CRY2 in skeletal muscle regeneration.
• To elucidate the molecular mechanisms by which CRY2 affects satellite cells.

Main Methods:

• Utilized skeletal muscle and satellite cell-specific CRY2 knockout mice (CRY2^scko).
• Performed single myofiber analysis and immunostaining.
• Analyzed the ERK1/2 signaling pathway and ETS1 transcription factor.

Main Results:

• CRY2 deletion significantly enhanced muscle regeneration.
• Loss of CRY2 increased myoblast proliferation and differentiation, evidenced by MyHC expression and myotube formation.
• CRY2 deficiency led to increased PAX7⁺ reserve cells and improved myoblast survival in ischemic conditions.
• Activated ERK1/2 and ETS1 signaling pathways were observed in CRY2-deficient myoblasts.

Conclusions:

• CRY2 is a critical regulator that inhibits skeletal muscle regeneration.
• Removing CRY2 promotes satellite cell activation, proliferation, and differentiation.
• CRY2 deficiency enhances muscle repair through ERK1/2-ETS1-PAX7 pathway activation and improved cell survival.