Piezo1 Promotes Odontogenic Differentiation of Dental Pulp Stem Cells Under Stress Conditions

Objectives: Mechanical stimuli signals regulate the odontogenic differentiation of dental pulp stem cells (DPSCs), but they are difficult to apply in clinical treatment. Piezo1, a specific mechanically activated ion channel that mediates mechanical transduction, may serve as a potential target for r...

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Main Authors: Xiaxia Wang, Shaojie Dong, Qianqian Dong, Xuefei Sun
Format: Article
Language:English
Published: Elsevier 2025-06-01
Series:International Dental Journal
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Online Access:http://www.sciencedirect.com/science/article/pii/S0020653925000401
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author Xiaxia Wang
Shaojie Dong
Qianqian Dong
Xuefei Sun
author_facet Xiaxia Wang
Shaojie Dong
Qianqian Dong
Xuefei Sun
author_sort Xiaxia Wang
collection DOAJ
description Objectives: Mechanical stimuli signals regulate the odontogenic differentiation of dental pulp stem cells (DPSCs), but they are difficult to apply in clinical treatment. Piezo1, a specific mechanically activated ion channel that mediates mechanical transduction, may serve as a potential target for regulating mechanical signals. In the present study, we aimed to investigate the function and potential molecular mechanisms of Piezo1 in the odontogenic differentiation of DPSCs. Methods: Piezo1 expression in human dental pulp and DPSCs was detected by immunofluorescence or immunohistochemistry (IHC). The mechanotransduction of Piezo1 ion channels in DPSCs was determined by fluid shear stress (FSS) detection of calcium fluorescence intensity and whole-cell patch clamp detection. The role of Piezo1 in the odontogenic differentiation of DPSCs was detected by alizarin red staining and Western blotting under hydrostatic pressure (HP). The expression and distribution of the downstream molecules Piezo1, CaN, and YAP were detected through coimmunoprecipitation (co-IP), immunocytochemistry (ICC), and Western blot analysis. Results: The Piezo1 protein was positively expressed in human dental pulp samples, especially in the odontoblast layer. Increased Piezo1 expression was also detected after odontogenic differentiation of DPSCs in vitro. The fluorescence intensity of intracellular calcium ions (Ca2+i) increased rapidly with treatment with FSS or Yoda1 (a Piezo1-specific agonist) but did not significantly change after treatment with GsMTx4 (a Piezo1 antagonist) or BAPTA (an extracellular calcium ion chelating agent). A whole-cell patch clamp was used to record the inward current induced by mechanical stimulation of the DPSCs. After Yoda1 treatment, the peak current increased, but the currents nearly completely disappeared after pretreatment with GsMTx4. In addition, we found that blocking CaN or YAP reversed the ability of HP to promote DPSC odontogenic differentiation. Co-IP and ICC revealed that the CaN and YAP proteins colocalized and bound to each other in DPSCs. Conclusions: These findings indicated that the Piezo1 ion channel mediates the mechanical transduction of DPSCs. In addition, Piezo1 promotes odontogenic differentiation of DPSCs through the Ca2+/CaN/YAP signalling axis under HP, which provides effective intervention targets for mechanical stimulation-mediated regulation of reparative dentin and vital pulp preservation.
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spelling doaj-art-0c4b97cbb3e746da98fd440744b83a722025-08-20T03:09:12ZengElsevierInternational Dental Journal0020-65392025-06-017531885189610.1016/j.identj.2025.01.018Piezo1 Promotes Odontogenic Differentiation of Dental Pulp Stem Cells Under Stress ConditionsXiaxia Wang0Shaojie Dong1Qianqian Dong2Xuefei Sun3Key Laboratory of Shaanxi Province for Craniofacial Precision Medicine Research, College of Stomatology, Xi'an Jiaotong University, Xi'an, China; Clinical Research Center of Shaanxi Province for Dental and Maxillofacial Diseases, Department of Endodontics, College of Stomatology, Xi'an Jiaotong University, Xi'an, ChinaKey Laboratory of Shaanxi Province for Craniofacial Precision Medicine Research, College of Stomatology, Xi'an Jiaotong University, Xi'an, China; Clinical Research Center of Shaanxi Province for Dental and Maxillofacial Diseases, Department of Endodontics, College of Stomatology, Xi'an Jiaotong University, Xi'an, ChinaKey Laboratory of Shaanxi Province for Craniofacial Precision Medicine Research, College of Stomatology, Xi'an Jiaotong University, Xi'an, China; Clinical Research Center of Shaanxi Province for Dental and Maxillofacial Diseases, Department of Endodontics, College of Stomatology, Xi'an Jiaotong University, Xi'an, ChinaKey Laboratory of Shaanxi Province for Craniofacial Precision Medicine Research, College of Stomatology, Xi'an Jiaotong University, Xi'an, China; Clinical Research Center of Shaanxi Province for Dental and Maxillofacial Diseases, Department of Endodontics, College of Stomatology, Xi'an Jiaotong University, Xi'an, China; Corresponding author: Key Laboratory of Shaanxi Province for Craniofacial Precision Medicine Research, Clinical Research Center of Shaanxi Province for Dental and Maxillofacial Diseases; Department of Endodontics, College of Stomatology, Xi'an Jiaotong University, Xiwu road, Xincheng district, Xi'an 710000, China.Objectives: Mechanical stimuli signals regulate the odontogenic differentiation of dental pulp stem cells (DPSCs), but they are difficult to apply in clinical treatment. Piezo1, a specific mechanically activated ion channel that mediates mechanical transduction, may serve as a potential target for regulating mechanical signals. In the present study, we aimed to investigate the function and potential molecular mechanisms of Piezo1 in the odontogenic differentiation of DPSCs. Methods: Piezo1 expression in human dental pulp and DPSCs was detected by immunofluorescence or immunohistochemistry (IHC). The mechanotransduction of Piezo1 ion channels in DPSCs was determined by fluid shear stress (FSS) detection of calcium fluorescence intensity and whole-cell patch clamp detection. The role of Piezo1 in the odontogenic differentiation of DPSCs was detected by alizarin red staining and Western blotting under hydrostatic pressure (HP). The expression and distribution of the downstream molecules Piezo1, CaN, and YAP were detected through coimmunoprecipitation (co-IP), immunocytochemistry (ICC), and Western blot analysis. Results: The Piezo1 protein was positively expressed in human dental pulp samples, especially in the odontoblast layer. Increased Piezo1 expression was also detected after odontogenic differentiation of DPSCs in vitro. The fluorescence intensity of intracellular calcium ions (Ca2+i) increased rapidly with treatment with FSS or Yoda1 (a Piezo1-specific agonist) but did not significantly change after treatment with GsMTx4 (a Piezo1 antagonist) or BAPTA (an extracellular calcium ion chelating agent). A whole-cell patch clamp was used to record the inward current induced by mechanical stimulation of the DPSCs. After Yoda1 treatment, the peak current increased, but the currents nearly completely disappeared after pretreatment with GsMTx4. In addition, we found that blocking CaN or YAP reversed the ability of HP to promote DPSC odontogenic differentiation. Co-IP and ICC revealed that the CaN and YAP proteins colocalized and bound to each other in DPSCs. Conclusions: These findings indicated that the Piezo1 ion channel mediates the mechanical transduction of DPSCs. In addition, Piezo1 promotes odontogenic differentiation of DPSCs through the Ca2+/CaN/YAP signalling axis under HP, which provides effective intervention targets for mechanical stimulation-mediated regulation of reparative dentin and vital pulp preservation.http://www.sciencedirect.com/science/article/pii/S0020653925000401Piezo1DPSCsOdontogenic differentiationCaNMechanotransductionYAP
spellingShingle Xiaxia Wang
Shaojie Dong
Qianqian Dong
Xuefei Sun
Piezo1 Promotes Odontogenic Differentiation of Dental Pulp Stem Cells Under Stress Conditions
International Dental Journal
Piezo1
DPSCs
Odontogenic differentiation
CaN
Mechanotransduction
YAP
title Piezo1 Promotes Odontogenic Differentiation of Dental Pulp Stem Cells Under Stress Conditions
title_full Piezo1 Promotes Odontogenic Differentiation of Dental Pulp Stem Cells Under Stress Conditions
title_fullStr Piezo1 Promotes Odontogenic Differentiation of Dental Pulp Stem Cells Under Stress Conditions
title_full_unstemmed Piezo1 Promotes Odontogenic Differentiation of Dental Pulp Stem Cells Under Stress Conditions
title_short Piezo1 Promotes Odontogenic Differentiation of Dental Pulp Stem Cells Under Stress Conditions
title_sort piezo1 promotes odontogenic differentiation of dental pulp stem cells under stress conditions
topic Piezo1
DPSCs
Odontogenic differentiation
CaN
Mechanotransduction
YAP
url http://www.sciencedirect.com/science/article/pii/S0020653925000401
work_keys_str_mv AT xiaxiawang piezo1promotesodontogenicdifferentiationofdentalpulpstemcellsunderstressconditions
AT shaojiedong piezo1promotesodontogenicdifferentiationofdentalpulpstemcellsunderstressconditions
AT qianqiandong piezo1promotesodontogenicdifferentiationofdentalpulpstemcellsunderstressconditions
AT xuefeisun piezo1promotesodontogenicdifferentiationofdentalpulpstemcellsunderstressconditions