Insufficient Mechanical Loading Downregulates Piezo1 in Chondrocytes and Impairs Fracture Healing Through ApoE‐Induced Senescence
Insufficient mechanical loading impairs fracture healing; however, the underlying mechanisms remain unclear. Increasing evidence indicates that Piezo1 plays an important role in fracture healing, although the effect of Piezo1 on the endochondral ossification of chondrocytes has been overlooked. This study reports that mechanical unloading down-regulates the expression of Piezo1 in chondrocytes and leads to fracture nonunion. Single-cell sequencing of calluses revealed that specific deletion of Piezo1 in chondrocytes upregulated the expression of apolipoprotein E (ApoE) in hypertrophic chondrocytes, resulting in delayed cartilage-to-bone transition due to enhanced chondrocyte senescence. Based on these results, an injectable and thermosensitive hydrogel is developed, which released an ApoE antagonist in situ at the fracture site. This hydrogel effectively attenuated chondrocyte senescence and, thus, promoted cartilage-to-bone transition as well as the fracture healing process. Overall, this data provide a new perspective on the activity of chondrocytes in fracture healing and a new direction for the treatment of fracture nonunion caused by insufficient mechanical loading.
Authors
- Siming Jia (ORCID: https://orcid.org/0000-0001-6821-4433)
- Weiguo Zou (ORCID: https://orcid.org/0000-0003-2516-0302)
- Wei Tong (ORCID: https://orcid.org/0000-0001-9951-2273)
- Wei Chen (ORCID: https://orcid.org/0000-0001-5451-6430)
- Juan Wang (ORCID: https://orcid.org/0000-0002-2537-1348)
- Feng Chen (ORCID: https://orcid.org/0000-0002-5606-7429)
- Tao Zhang (ORCID: https://orcid.org/0000-0002-7257-5677)
- Mo Zhang (ORCID: https://orcid.org/0000-0003-3231-5915)
- Lijun Wang (ORCID: https://orcid.org/0000-0002-5613-2382)
- Yingze Zhang
- Weijian Liu (ORCID: https://orcid.org/0000-0002-2098-0515)
- Zhiyong Hou (ORCID: https://orcid.org/0000-0001-7858-2379)
- Hongzhi Lv (ORCID: https://orcid.org/0000-0003-1616-6243)
- Chuan Ren (ORCID: https://orcid.org/0000-0003-4559-9507)
Institutions
- Hebei Medical University (CN)
- Union Hospital (HK)
- Third Hospital of Hebei Medical University (CN)
- Center for Excellence in Molecular Cell Science (CN)
- Wuhan Union Hospital (CN)
- University of Chinese Academy of Sciences (CN)
- Huazhong University of Science and Technology (CN)
- Hainan Medical University (CN)
Publication Details
- Journal
- Advanced Science
- Published
- 2024-10-17
- DOI
- https://doi.org/10.1002/advs.202400502
- Citations
- 14
- Primary Topic
- Erythrocyte Function and Pathophysiology
- Type
- article
- Field-Weighted Citation Impact
- 4.57
Funders
- National Natural Science Foundation of China
- Chinese Academy of Sciences
- Natural Science Foundation of Hebei Province
- University of Chinese Academy of Sciences
- Hebei Medical University
- National Key Research and Development Program of China