Role of YAP in Odontoblast Damage Repair in a Dentin Hypersensitivity Model

• Published in: International dental journal Vol. 74; no. 3; pp. 597 - 606
• Main Authors: Tong, Xiangyao, Wang, Yijie, Zhang, Hui, Liu, Peiqi, Wang, Chenxu, Liu, Huizhe, Zou, Rui, Niu, Lin
• Format: Journal Article
• Language: English
• Published: England Elsevier 01.06.2024
• Subjects: Adaptor Proteins, Signal Transducing - metabolism; Animals; Damage repair; Dentin hypersensitivity; Dentin Sensitivity; Disease Models, Animal; Extracellular Matrix Proteins - metabolism; Fluid shear stress; Immunohistochemistry; Integrin alphaVbeta3 - metabolism; Ion Channels - metabolism; Male; Membrane Proteins; Odontoblasts; Odontoblasts - metabolism; Phosphoproteins - metabolism; Rats; Rats, Sprague-Dawley; Sialoglycoproteins - metabolism; Stress, Mechanical; Verteporfin - pharmacology; Verteporfin - therapeutic use; YAP; YAP-Signaling Proteins; YAP; Damage repair; Fluid shear stress; Odontoblasts; Dentin hypersensitivity
• ISSN: 0020-6539; 1875-595X; 1875-595X
• DOI: 10.1016/j.identj.2023.11.003

The aim of this study was to investigate the molecular mechanism underlying odontoblast damage repair in dentin hypersensitivity (DH) and the role of Yes-associated protein (YAP) in this process. The DH model was constructed in Sprague-Dawley (SD) rats, and the in vivo expression of Piezo1, Integrin αvβ3, YAP, and dentin sialophosphoprotein (DSPP) was detected by immunohistochemistry. COMSOL Multiphysics software was used to simulate the dentinal tubule fluid flow velocity and corresponding fluid shear stress (FSS) on the odontoblast processes. MDPC-23 cells were cultured in vitro and loaded with a peristaltic pump for 1 hour at FSS values of 0.1, 0.3, 0.5, and 0.7 dyne/cm . The expression of Piezo1, Integrin αvβ3, and YAP was detected by immunofluorescence. Verteporfin (a YAP-specific inhibitor) was utilised to confirm the effect of YAP on the expression of dentineogenesis-related protein under FSS. The level and duration of external mechanical stimuli have an effect on the functional expression of odontoblasts. In DH, the harder the food that is chewed, the faster the flow of the dentinal tubule fluid and the greater the FSS on the odontoblast processes. The expression of Piezo1, Integrin αvβ3, and YAP can be promoted when the FSS is less than 0.3 dyne/cm . After YAP inhibition, the DSPP protein expression level was reduced at 0.3 dyne/cm FSS. These results suggest that appropriate FSS can enhance the expression of odontoblast-related factors in odontoblasts via the Piezo1-Integrin αvβ3-YAP mechanotransduction pathway and the YAP appears to play an essential role in the response of odontoblasts to external mechanical stimuli.