Role of TRPC6 in periodontal tissue reconstruction mediated by appropriate stress

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

doi:10.1186/s13287-022-03055-z

Role of TRPC6 in periodontal tissue reconstruction mediated by appropriate stress

Stem Cell Res Ther. 2022 Aug 5;13(1):401. doi: 10.1186/s13287-022-03055-z.

Authors

Li Wang^#^{1

2

3}, Hong Liang^#⁴, Bingjing Sun^{1

2}, Jing Mi^{1

2}, Xianqin Tong^{1

2}, Yuhui Wang^{1

2}, Meihua Chen^{1

2}, Liming Yu^{1

2}, Jie Pan^{1

2}, Shangfeng Liu⁵, Yan-Jun Liu⁶, Yuehua Liu^{7

8}

Affiliations

¹ Department of Orthodontics, Shanghai Stomatological Hospital, Fudan University, Shanghai, China.
² Shanghai Key Laboratory of Craniomaxillofacial Development and Diseases, Shanghai Stomatological Hospital, Fudan University, Shanghai, 200001, China.
³ Dental Department, Shanghai 1st People's Hospital Affiliated to Shanghai Jiao Tong University, Shanghai, China.
⁴ Shanghai 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 University, Shanghai, 200032, China.
⁵ Shanghai Key Laboratory of Craniomaxillofacial Development and Diseases, Shanghai Stomatological Hospital, Fudan University, Shanghai, 200001, China. Shangfeng_liu683@fudan.edu.en.
⁶ Shanghai 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 University, Shanghai, 200032, China. Yanjun_Liu@fudan.edu.cn.
⁷ Department of Orthodontics, Shanghai Stomatological Hospital, Fudan University, Shanghai, China. liuyuehua@fudan.edu.cn.
⁸ Shanghai Key Laboratory of Craniomaxillofacial Development and Diseases, Shanghai Stomatological Hospital, Fudan University, Shanghai, 200001, China. liuyuehua@fudan.edu.cn.

^# Contributed equally.

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. 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.

Keywords: A confined microenvironment; Mechanical force; Periodontal ligament stem cells; TRPC6; TRPC6 −/− mice.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Cell Differentiation / physiology
Humans
Mesenchymal Stem Cells* / metabolism
Mice
Osteogenesis / physiology
Periodontal Ligament*
Stem Cells / metabolism
TRPC6 Cation Channel / metabolism
Tooth Movement Techniques

Substances

TRPC6 Cation Channel
TRPC6 protein, human
Trpc6 protein, mouse