2. Academic Validation
  3. The Sirt1-Piezo1 Axis Promotes Bone Formation and Repair in Mice

The Sirt1-Piezo1 Axis Promotes Bone Formation and Repair in Mice

  • Adv Sci (Weinh). 2025 Sep 26:e10103. doi: 10.1002/advs.202510103.
Donghao Gan 1,  Yi Ran 1,  Hong Pan 2 3,  Qinnan Yan 1,  Wenjing Zhang 4,  Bo Zhou 1,  Pengzhi Xu 5,  Rongdong Liao 1 6,  Haipeng Xue 7,  Will Jiang 8,  Tailin He 1,  Qingyun Jia 5,  Lei Qin 9,  Francis Y Lee 8,  Di Chen 10,  Chuanju Liu 8,  Guozhi Xiao 1
Affiliations

Affiliations

  • 1 Department of Biochemistry, Homeostatic Medicine Institute, School of Medicine, Guangdong Provincial Key Laboratory of Cell Microenvironment and Disease Research, Shenzhen Key Laboratory of Cell Microenvironment, Southern University of Science and Technology, Shenzhen, 518055, China.
  • 2 Guangdong Key Laboratory of Nanomedicine, CAS-HK Joint Lab of Biomaterials, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, 518055, China.
  • 3 University of Chinese Academy of Sciences, Beijing, 101408, China.
  • 4 School of Medicine, Shenzhen University, Shenzhen, 518055, China.
  • 5 Department of Orthopedics, Linyi People's Hospital, Linyi, 276800, China.
  • 6 Department of Joint and Orthopedics, Zhujiang Hospital, Southern Medical University, Guangzhou, 510282, China.
  • 7 Department of Orthopedics, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, 250014, China.
  • 8 Department of Orthopaedics & Rehabilitation, Yale University School of Medicine, New Haven, 06510, USA.
  • 9 Department of Orthopedics, Huazhong University of Science and Technology Union Shenzhen Hospital, Shenzhen, 518000, China.
  • 10 Faculty of Pharmaceutical Sciences, Shenzhen University of Advanced Technology, Shenzhen, 518107, China.
PMID: 40999873 DOI: 10.1002/advs.202510103
Abstract

The mechanosensitive Piezo1 channel protein plays a pivotal role in promoting bone formation and repair; however, its underlying molecular mechanism(s) are poorly defined. Here this study shows that SIRT1 positively regulates Piezo1 expression and activity to promote osteogenesis and bone repair in mice. This study finds that Piezo1 is up-regulated in the cartilage callus during bone repair. Deleting Piezo1 in chondrocytes largely impairs endochondral ossification and mechanically induced osteogenesis and delays fracture healing in mice, while Yoda1 activation of Piezo1 exerts opposite effects. SIRT1 overexpression or activation dramatically increases Piezo1 protein expression in a dose-dependent manner. SIRT1 binds to Piezo1 protein and deacetylates and activates Piezo1 and CA2+ influx in chondrocytes. Piezo1 loss in chondrocytes abolishes the ability of SIRT1 Activator SRT2104 to accelerate bone repair. Resveratrol (RSV), a natural SIRT1 Activator, also potently activates Piezo1 and enhances bone repair. A yeast microcapsule-based oral formulation of RSV (YC-RSV) is developed to improve drug bioavailability and therapeutic efficacy, which highly and selectively targets to the inflammatory fracture site. Thus, it demonstrates that SIRT1 is a novel and potent activator of Piezo1 to promote bone formation and repair, supporting the potential clinical application of SIRT1 activators in promoting bone formation and repair.

Keywords

Piezo1; Sirt1; bone repair; chondrocytes; deacetylation; osteogenesis.

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