Role of TRPC6 in periodontal tissue reconstruction mediated by appropriate stress

Abstract Introduction The basis of orthodontic tooth movement (OTM) is the reconstruction of periodontal tissue under stress. Increasing the speed of OTM has always been the focus of attention. Objectives Periodontal ligament stem cells (PDLSCs) are direct effector cells of mechanical force, but the...

Full description

Bibliographic Details
Main Authors: Li Wang, Hong Liang, Bingjing Sun, Jing Mi, Xianqin Tong, Yuhui Wang, Meihua Chen, Liming Yu, Jie Pan, Shangfeng Liu, Yan-Jun Liu, Yuehua Liu
Format: Article
Language:English
Published: BMC 2022-08-01
Series:Stem Cell Research & Therapy
Subjects:
Online Access:https://doi.org/10.1186/s13287-022-03055-z
_version_ 1811315273743990784
author Li Wang
Hong Liang
Bingjing Sun
Jing Mi
Xianqin Tong
Yuhui Wang
Meihua Chen
Liming Yu
Jie Pan
Shangfeng Liu
Yan-Jun Liu
Yuehua Liu
author_facet Li Wang
Hong Liang
Bingjing Sun
Jing Mi
Xianqin Tong
Yuhui Wang
Meihua Chen
Liming Yu
Jie Pan
Shangfeng Liu
Yan-Jun Liu
Yuehua Liu
author_sort Li Wang
collection DOAJ
description Abstract Introduction The basis of orthodontic tooth movement (OTM) is the reconstruction of periodontal tissue under stress. Increasing the speed of OTM has always been the focus of attention. Objectives Periodontal ligament stem cells (PDLSCs) are direct effector cells of mechanical force, but the mechanism by which PDLSCs sense mechanical stimuli is unclear. Methods Human PDLSCs (hPDLSCs) were analyzed in the presence or absence of force loading with the Flexcell loading system in vitro. Then, periodontal tissues were analyzed after mechanical stimulation in vivo. In addition, cells in a confined microenvironment were analyzed to observe changes in the cytoskeleton and migration. Finally, TRPC6−/− mice were used to further verify the effect of TRPC6. After force application, the OTM distance, bone marrow density (BMD), TRPC6 and COL1 expression, and TRAP staining were evaluated in periodontal tissues. Results RNA sequencing (RNA-seq) and western blot analyses revealed that TRPC6 was important during mechanical force application to hPDLSCs. Appropriate mechanical force application also induced TRPC6 activation in the OTM model and the confined microenvironment. Under a slightly confined microenvironment, treatment with the TRPC6 inhibitor SKF96365 and TRPC6 knockout decreased the migration speed of hPDLSCs and mouse bone marrow mesenchymal stem cells (mBMSCs). In addition, TRPC6−/− mice showed lower OTM distances and reduced osteogenic and osteoclastic differentiation. Conclusion In summary, TRPC6 activation in PDLSCs mediated by appropriate mechanical force application contributes to periodontal tissue reconstruction. Graphical abstract PDLSCs modulate periodontal tissue remodeling under appropriate mechanical stimulation through TRPC6; however, under excessive stress, alveolar bone and tooth roots are readily absorbed. Under this condition, environmental factors play a leading role, and the regulatory effect of TRPC6 is not obvious.
first_indexed 2024-04-13T11:28:28Z
format Article
id doaj.art-3db9433576024a12882c8916f5e02aa4
institution Directory Open Access Journal
issn 1757-6512
language English
last_indexed 2024-04-13T11:28:28Z
publishDate 2022-08-01
publisher BMC
record_format Article
series Stem Cell Research & Therapy
spelling doaj.art-3db9433576024a12882c8916f5e02aa42022-12-22T02:48:38ZengBMCStem Cell Research & Therapy1757-65122022-08-0113111510.1186/s13287-022-03055-zRole of TRPC6 in periodontal tissue reconstruction mediated by appropriate stressLi Wang0Hong Liang1Bingjing Sun2Jing Mi3Xianqin Tong4Yuhui Wang5Meihua Chen6Liming Yu7Jie Pan8Shangfeng Liu9Yan-Jun Liu10Yuehua Liu11Department of Orthodontics, Shanghai Stomatological Hospital, Fudan UniversityShanghai Key Laboratory of Medical Epigenetics, International Co-Laboratory of Medical Epigenetics and Metabolism (Ministry of Science and Technology), Institutes of Biomedical Sciences, Department of Systems Biology for Medicine, Fudan UniversityDepartment of Orthodontics, Shanghai Stomatological Hospital, Fudan UniversityDepartment of Orthodontics, Shanghai Stomatological Hospital, Fudan UniversityDepartment of Orthodontics, Shanghai Stomatological Hospital, Fudan UniversityDepartment of Orthodontics, Shanghai Stomatological Hospital, Fudan UniversityDepartment of Orthodontics, Shanghai Stomatological Hospital, Fudan UniversityDepartment of Orthodontics, Shanghai Stomatological Hospital, Fudan UniversityDepartment of Orthodontics, Shanghai Stomatological Hospital, Fudan UniversityShanghai Key Laboratory of Craniomaxillofacial Development and Diseases, Shanghai Stomatological Hospital, Fudan UniversityShanghai Key Laboratory of Medical Epigenetics, International Co-Laboratory of Medical Epigenetics and Metabolism (Ministry of Science and Technology), Institutes of Biomedical Sciences, Department of Systems Biology for Medicine, Fudan UniversityDepartment of Orthodontics, Shanghai Stomatological Hospital, Fudan UniversityAbstract Introduction The basis of orthodontic tooth movement (OTM) is the reconstruction of periodontal tissue under stress. Increasing the speed of OTM has always been the focus of attention. Objectives Periodontal ligament stem cells (PDLSCs) are direct effector cells of mechanical force, but the mechanism by which PDLSCs sense mechanical stimuli is unclear. Methods Human PDLSCs (hPDLSCs) were analyzed in the presence or absence of force loading with the Flexcell loading system in vitro. Then, periodontal tissues were analyzed after mechanical stimulation in vivo. In addition, cells in a confined microenvironment were analyzed to observe changes in the cytoskeleton and migration. Finally, TRPC6−/− mice were used to further verify the effect of TRPC6. After force application, the OTM distance, bone marrow density (BMD), TRPC6 and COL1 expression, and TRAP staining were evaluated in periodontal tissues. Results RNA sequencing (RNA-seq) and western blot analyses revealed that TRPC6 was important during mechanical force application to hPDLSCs. Appropriate mechanical force application also induced TRPC6 activation in the OTM model and the confined microenvironment. Under a slightly confined microenvironment, treatment with the TRPC6 inhibitor SKF96365 and TRPC6 knockout decreased the migration speed of hPDLSCs and mouse bone marrow mesenchymal stem cells (mBMSCs). In addition, TRPC6−/− mice showed lower OTM distances and reduced osteogenic and osteoclastic differentiation. Conclusion In summary, TRPC6 activation in PDLSCs mediated by appropriate mechanical force application contributes to periodontal tissue reconstruction. Graphical abstract PDLSCs modulate periodontal tissue remodeling under appropriate mechanical stimulation through TRPC6; however, under excessive stress, alveolar bone and tooth roots are readily absorbed. Under this condition, environmental factors play a leading role, and the regulatory effect of TRPC6 is not obvious.https://doi.org/10.1186/s13287-022-03055-zTRPC6Mechanical forcePeriodontal ligament stem cellsTRPC6 −/− miceA confined microenvironment
spellingShingle Li Wang
Hong Liang
Bingjing Sun
Jing Mi
Xianqin Tong
Yuhui Wang
Meihua Chen
Liming Yu
Jie Pan
Shangfeng Liu
Yan-Jun Liu
Yuehua Liu
Role of TRPC6 in periodontal tissue reconstruction mediated by appropriate stress
Stem Cell Research & Therapy
TRPC6
Mechanical force
Periodontal ligament stem cells
TRPC6 −/− mice
A confined microenvironment
title Role of TRPC6 in periodontal tissue reconstruction mediated by appropriate stress
title_full Role of TRPC6 in periodontal tissue reconstruction mediated by appropriate stress
title_fullStr Role of TRPC6 in periodontal tissue reconstruction mediated by appropriate stress
title_full_unstemmed Role of TRPC6 in periodontal tissue reconstruction mediated by appropriate stress
title_short Role of TRPC6 in periodontal tissue reconstruction mediated by appropriate stress
title_sort role of trpc6 in periodontal tissue reconstruction mediated by appropriate stress
topic TRPC6
Mechanical force
Periodontal ligament stem cells
TRPC6 −/− mice
A confined microenvironment
url https://doi.org/10.1186/s13287-022-03055-z
work_keys_str_mv AT liwang roleoftrpc6inperiodontaltissuereconstructionmediatedbyappropriatestress
AT hongliang roleoftrpc6inperiodontaltissuereconstructionmediatedbyappropriatestress
AT bingjingsun roleoftrpc6inperiodontaltissuereconstructionmediatedbyappropriatestress
AT jingmi roleoftrpc6inperiodontaltissuereconstructionmediatedbyappropriatestress
AT xianqintong roleoftrpc6inperiodontaltissuereconstructionmediatedbyappropriatestress
AT yuhuiwang roleoftrpc6inperiodontaltissuereconstructionmediatedbyappropriatestress
AT meihuachen roleoftrpc6inperiodontaltissuereconstructionmediatedbyappropriatestress
AT limingyu roleoftrpc6inperiodontaltissuereconstructionmediatedbyappropriatestress
AT jiepan roleoftrpc6inperiodontaltissuereconstructionmediatedbyappropriatestress
AT shangfengliu roleoftrpc6inperiodontaltissuereconstructionmediatedbyappropriatestress
AT yanjunliu roleoftrpc6inperiodontaltissuereconstructionmediatedbyappropriatestress
AT yuehualiu roleoftrpc6inperiodontaltissuereconstructionmediatedbyappropriatestress