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

Skeletal muscle has remarkable capacity to regenerate upon injury due to the presence of satellite cells. The maintenance and function of satellite cells are regulated by circadian clock. Cryptocrhome 2 (CRY2) is a key component of the circadian clock and its role in skeletal muscle regeneration remains controversial. Here, we report that CRY2 is down-regulated during muscle regeneration. Using the satellite cell specific CRY2 knockout mice (CRY2scko), we show that deletion of CRY2 enhances muscle regeneration. Single myofiber analysis showed that deletion of CRY2 enhances satellite cell self-renewal. In the absence of CRY2, the ERK1/2 and JNK1/2 signaling pathways become activated, which phosphorylates the transcription factor ETS1, which in turn binds to the promoter of PAX7 to induce its transcription. CRY2 deficient myoblasts survived better in ischemic muscle. Deletion of CRY2 also alleviated myopathy in mdx mice. Therefore, CRY2 plays an essential role in regulating satellite cell function and skeletal muscle regeneration. Total RNA from 8-week old CRY2flox mouse and CRY2scko mouse.