2. Academic Validation
  3. Circadian rhythm modulates endochondral bone formation via MTR1/AMPKβ1/BMAL1 signaling axis

Circadian rhythm modulates endochondral bone formation via MTR1/AMPKβ1/BMAL1 signaling axis

  • Cell Death Differ. 2022 Apr;29(4):874-887. doi: 10.1038/s41418-021-00919-4.
Shaoling Yu  # 1 2 3,  Qingming Tang  # 1 2 3,  Guangjin Chen 1 2 3,  Xiaofeng Lu 1 2 3,  Ying Yin 1 2 3,  Mengru Xie 1 2 3,  Yanlin Long 1 2 3,  Wenhao Zheng 1 2 3,  Fengyuan Guo 1 2 3,  Longquan Shao 4,  Anbing Shi 5,  Lili Chen 6 7 8
Affiliations

Affiliations

  • 1 Department of Stomatology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
  • 2 School of Stomatology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
  • 3 Hubei Province Key Laboratory of Oral and Maxillofacial Development and Regeneration, Wuhan, 430022, China.
  • 4 Stomatological Hospital, Southern Medical University, Guangzhou, 510280, China.
  • 5 Department of Medical Genetics, School of Basic Medicine and the Collaborative Innovation Center for Brain Science, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
  • 6 Department of Stomatology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China. chenlili1030@hust.edu.cn.
  • 7 School of Stomatology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China. chenlili1030@hust.edu.cn.
  • 8 Hubei Province Key Laboratory of Oral and Maxillofacial Development and Regeneration, Wuhan, 430022, China. chenlili1030@hust.edu.cn.
  • # Contributed equally.
PMID: 35094018 DOI: 10.1038/s41418-021-00919-4
Abstract

The circadian clock is a master regulator in coordinating daily oscillations of physiology and behaviors. Nevertheless, how the circadian rhythm affects endochondral ossification is poorly understood. Here we showed that endochondral bone formation exhibits circadian rhythms, manifested as fast DNA replication in the daytime, active cell mitosis, and matrix synthesis at night. Circadian rhythm disruption led to endochondral ossification deformities. The mechanistic dissection revealed that Melatonin Receptor 1 (MTR1) periodically activates the AMPKβ1 phosphorylation, which then orchestrates the rhythms of cell proliferation and matrix synthesis via destabilizing the clock component CRY1 and triggering BMAL1 expression. Accordingly, the AMPKβ1 agonist is capable of alleviating the abnormity of endochondral ossification caused by circadian dysrhythmias. Taken together, these findings indicated that the central circadian clock could control endochondral bone formation via the MTR1/AMPKβ1/BMAL1 signaling axis in chondrocytes. Also, our results suggested that the AMPKβ1 signaling activators are promising medications toward endochondral ossification deformities.

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