Department of Orthodontics, Shanghai Stomatological Hospital, Fudan University, Shanghai, China.
Shanghai Key Laboratory of Craniomaxillofacial Development and Diseases, Shanghai Stomatological Hospital, Fudan University, Shanghai, 200001, China.
Stem Cell Res Ther. 2022 Aug 5;13(1):401. doi: 10.1186/s13287-022-03055-z.
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.
Periodontal ligament stem cells (PDLSCs) are direct effector cells of mechanical force, but the mechanism by which PDLSCs sense mechanical stimuli is unclear.
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.
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.
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.
正畸牙齿移动（OTM）的基础是在应力下重建牙周组织。增加 OTM 的速度一直是关注的焦点。
牙周韧带干细胞（PDLSCs）是机械力的直接效应细胞，但 PDLSCs 感知机械刺激的机制尚不清楚。
体外使用 Flexcell 加载系统分析有或没有力加载的人牙周膜干细胞（hPDLSCs）。然后，在体内进行机械刺激后分析牙周组织。此外，分析处于受限微环境中的细胞，观察细胞骨架和迁移的变化。最后，使用 TRPC6 小鼠进一步验证 TRPC6 的作用。施加力后，评估牙周组织中的 OTM 距离、骨髓密度（BMD）、TRPC6 和 COL1 表达以及 TRAP 染色。
RNA 测序（RNA-seq）和 Western blot 分析表明，TRPC6 在 hPDLSCs 受到机械力作用时很重要。适当的机械力应用也诱导 OTM 模型和受限微环境中的 TRPC6 激活。在略微受限的微环境下，用 TRPC6 抑制剂 SKF96365 和 TRPC6 敲除处理会降低 hPDLSCs 和小鼠骨髓间充质干细胞（mBMSCs）的迁移速度。此外，TRPC6 小鼠的 OTM 距离较低，成骨和破骨分化减少。
总之，适当机械力作用下 PDLSCs 中的 TRPC6 激活有助于牙周组织重建。PDLSCs 通过 TRPC6 调节适当机械刺激下的牙周组织重塑；然而，在过度的压力下，牙槽骨和牙根很容易被吸收。在这种情况下，环境因素起主导作用，TRPC6 的调节作用不明显。
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