Abstract

Introduction This study aims to investigate the role of Piezo1 in temporomandibular joint (TMJ) condylar bone remodeling under mechanical stimulation in orthodontic treatment. Methods Piezo1 flox/flox ; Col2α1-Cre + (Piezo1 Col2α1 KO) and Piezo1 flox/flox ; Col2α1-Cre - (Control) mice were generated for in vivo study. A mandibular advancement (MA) model was established to induce bone remodeling in TMJ condyle. Subchondral bone quality was assessed using micro-CT, while changes in the distribution and expression levels of Piezo1, Osx, and Ocn were evaluated via immunofluorescence staining. In vitro, ATDC5 cells were subjected to 6% cyclic tensile strain (CTS) using Flexcell 5000 T. ShPiezo1 ATDC5 model was constructed by lentiviral transfection. The influence of Piezo1 on osteogenic markers and PI3K/Akt pathway under CTS was evaluated through a real-time polymerase chain reaction analysis and Western blot. An Akt agonist (SC79) was used to observe the rescue effect of Akt activation on experiments carried out on ShPiezo1 cells under CTS, and the protein expression of Akt, pAkt, Osx, and Ocn was detected by Western blot. Results Piezo1, Osx and Ocn were overexpressed in the MA-induced condylar cartilage and ATDC5 under CTS. Conditional knockout of Piezo1 inhibited the bone remodeling of TMJ condylar cartilage in mice. Piezo1 silencing suppressed osteogenic marker expression and PI3K/Akt signaling in CTS-stimulated ATDC5 cells, which was partially rescued by treatment with SC79. Conclusions Piezo1 is essential for mechanical stimulation–induced bone remodeling in TMJ condylar cartilage. Under CTS, Piezo1 mediates the upregulation of osteogenic markers in chondrocytes via activation of PI3K/Akt pathway, highlighting its potential as a mechanotherapeutic target in craniofacial bone regeneration.