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

SUBMITTER: Jia S 

PROVIDER: S-EPMC11633519 | biostudies-literature | 2024 Dec

REPOSITORIES: biostudies-literature