Loss of CRY2 promotes regenerative myogenesis by enhancing PAX7 expression and satellite cell proliferation
Yingxue Hao,
Ting Xue,
Song‐Bai Liu,
Sha Geng,
Xinghong Shi,
Panting Qian,
Wei He,
Jiqing Zheng,
Yanfang Li,
Jing Lou,
Tianze Shi,
Ge Wang,
Xiaoxiao Wang,
Yanli Wang,
Yangxin Li,
Yao‐Hua Song
Affiliations
Yingxue Hao
Cyrus Tang Hematology Center Collaborative Innovation Center of Hematology Soochow University Suzhou P. R. China
Ting Xue
Cyrus Tang Hematology Center Collaborative Innovation Center of Hematology Soochow University Suzhou P. R. China
Song‐Bai Liu
Suzhou Vocational Health College, Suzhou Key Laboratory of Biotechnology for Laboratory Medicine Suzhou Jiangsu P. R. China
Sha Geng
Cyrus Tang Hematology Center Collaborative Innovation Center of Hematology Soochow University Suzhou P. R. China
Xinghong Shi
Cyrus Tang Hematology Center Collaborative Innovation Center of Hematology Soochow University Suzhou P. R. China
Panting Qian
Cyrus Tang Hematology Center Collaborative Innovation Center of Hematology Soochow University Suzhou P. R. China
Wei He
Cyrus Tang Hematology Center Collaborative Innovation Center of Hematology Soochow University Suzhou P. R. China
Jiqing Zheng
Cyrus Tang Hematology Center Collaborative Innovation Center of Hematology Soochow University Suzhou P. R. China
Yanfang Li
Cyrus Tang Hematology Center Collaborative Innovation Center of Hematology Soochow University Suzhou P. R. China
Jing Lou
Cyrus Tang Hematology Center Collaborative Innovation Center of Hematology Soochow University Suzhou P. R. China
Tianze Shi
Cyrus Tang Hematology Center Collaborative Innovation Center of Hematology Soochow University Suzhou P. R. China
Ge Wang
Cyrus Tang Hematology Center Collaborative Innovation Center of Hematology Soochow University Suzhou P. R. China
Xiaoxiao Wang
Suzhou Vocational Health College, Suzhou Key Laboratory of Biotechnology for Laboratory Medicine Suzhou Jiangsu P. R. China
Yanli Wang
Institute for Cardiovascular Science and Department of Cardiovascular Surgery First Affiliated Hospital and Medical College of Soochow University Suzhou Jiangsu P. R. China
Yangxin Li
Institute for Cardiovascular Science and Department of Cardiovascular Surgery First Affiliated Hospital and Medical College of Soochow University Suzhou Jiangsu P. R. China
Yao‐Hua Song
Cyrus Tang Hematology Center Collaborative Innovation Center of Hematology Soochow University Suzhou P. R. China
Abstract The regenerative capacity of skeletal muscle is dependent on satellite cells. The circadian clock regulates the maintenance and function of satellite cells. Cryptochrome 2 (CRY2) is a critical component of the circadian clock, and its role in skeletal muscle regeneration remains controversial. Using the skeletal muscle lineage and satellite cell‐specific CRY2 knockout mice (CRY2scko), we show that the deletion of CRY2 enhances muscle regeneration. Single myofiber analysis revealed that deletion of CRY2 stimulates the proliferation of myoblasts. The differentiation potential of myoblasts was enhanced by the loss of CRY2 evidenced by increased expression of myosin heavy chain (MyHC) and myotube formation in CRY2−/− cells versus CRY2+/+ cells. Immunostaining revealed that the number of mononucleated paired box protein 7 (PAX7+) cells associated with myotubes formed by CRY2−/− cells was increased compared with CRY2+/+ cells, suggesting that more reserve cells were produced in the absence of CRY2. Loss of CRY2 leads to the activation of the ERK1/2 signaling pathway and ETS1, which binds to the promoter of PAX7 to induce its transcription. CRY2 deficient myoblasts survived better in ischemic muscle. Therefore, CRY2 is essential in regulating skeletal muscle repair.
