Insufficient Mechanical Loading Downregulates Piezo1 in Chondrocytes and Impairs Fracture Healing Through ApoE‐Induced Senescence
Abstract: 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.
- Location
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Deutsche Nationalbibliothek Frankfurt am Main
- Extent
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Online-Ressource
- Language
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Englisch
- Bibliographic citation
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Insufficient Mechanical Loading Downregulates Piezo1 in Chondrocytes and Impairs Fracture Healing Through ApoE‐Induced Senescence ; day:17 ; month:10 ; year:2024 ; extent:16
Advanced science ; (17.10.2024) (gesamt 16)
- Creator
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Jia, Siming
Liu, Weijian
Zhang, Mo
Wang, Lijun
Ren, Chuan
Feng, Chen
Zhang, Tao
Lv, Hongzhi
Hou, Zhiyong
Zou, Weiguo
Zhang, Yingze
Tong, Wei
Wang, Juan
Chen, Wei
- DOI
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10.1002/advs.202400502
- URN
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urn:nbn:de:101:1-2410181430161.321507079009
- Rights
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Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
- Last update
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15.09.2027, 7:05 AM CEST
Data provider
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Associated
- Jia, Siming
- Liu, Weijian
- Zhang, Mo
- Wang, Lijun
- Ren, Chuan
- Feng, Chen
- Zhang, Tao
- Lv, Hongzhi
- Hou, Zhiyong
- Zou, Weiguo
- Zhang, Yingze
- Tong, Wei
- Wang, Juan
- Chen, Wei
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