Heavy mechanical force decelerates orthodontic tooth movement via Piezo1-induced mitochondrial calcium down-regulation
Orthodontic tooth movement (OTM) depends on periodontal ligament cells (PDLCs), which sense biomechanical stimuli and initiate alveolar bone remodeling. Light (optimal) forces accelerate OTM, whereas heavy forces decelerate it. However, the mechanisms by which PDLCs sense biomechanical stimuli and a...
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KeAi Communications Co., Ltd.
2025-03-01
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| Series: | Genes and Diseases |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2352304224002319 |
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| author | Ye Zhu Xuehuan Meng Qiming Zhai Liangjing Xin Hao Tan Xinyi He Xiang Li Guoyin Yang Jinlin Song Leilei Zheng |
| author_facet | Ye Zhu Xuehuan Meng Qiming Zhai Liangjing Xin Hao Tan Xinyi He Xiang Li Guoyin Yang Jinlin Song Leilei Zheng |
| author_sort | Ye Zhu |
| collection | DOAJ |
| description | Orthodontic tooth movement (OTM) depends on periodontal ligament cells (PDLCs), which sense biomechanical stimuli and initiate alveolar bone remodeling. Light (optimal) forces accelerate OTM, whereas heavy forces decelerate it. However, the mechanisms by which PDLCs sense biomechanical stimuli and affect osteoclastic activities under different mechanical forces (MFs) remain unclear. This study demonstrates that mechanosensitive ion channel Piezo1-mediated Ca2+ signal conversion is crucial for sensing and delivering biomechanical signals in PDLCs under heavy-force conditions. Heavy MF up-regulated Piezo1 in PDLCs, reducing mitochondrial Ca2+ influx by inhibiting ITPR3 expression in mitochondria-associated membranes. Decreased mitochondrial calcium uptake led to reduced cytoplasmic release of mitochondrial DNA and inhibited the activation of the cGAS‒STING signaling cascade, subsequently inhibiting monocyte-to-osteoclast differentiation. Inhibition of Piezo1 or up-regulation of STING expression under heavy MF conditions significantly increased osteoclast activity and accelerated OTM. These findings suggest that heavy MF-induced Piezo1 expression in PDLCs is closely related to the control of osteoclast activity during OTM and plays an essential role in alveolar bone remodeling. This mechanism may be a potential therapeutic target for accelerating OTM. |
| format | Article |
| id | doaj-art-9c8ff71ea45347f6ac031f1a6f269612 |
| institution | Kabale University |
| issn | 2352-3042 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | KeAi Communications Co., Ltd. |
| record_format | Article |
| series | Genes and Diseases |
| spelling | doaj-art-9c8ff71ea45347f6ac031f1a6f2696122024-12-26T08:56:34ZengKeAi Communications Co., Ltd.Genes and Diseases2352-30422025-03-01122101434Heavy mechanical force decelerates orthodontic tooth movement via Piezo1-induced mitochondrial calcium down-regulationYe Zhu0Xuehuan Meng1Qiming Zhai2Liangjing Xin3Hao Tan4Xinyi He5Xiang Li6Guoyin Yang7Jinlin Song8Leilei Zheng9College of Stomatology, Chongqing Medical University, Chongqing Key Laboratory of Oral Diseases, Chongqing Municipal Key Laboratory of Oral Biomedical Engineering of Higher Education, Chongqing 401147, ChinaCollege of Stomatology, Chongqing Medical University, Chongqing Key Laboratory of Oral Diseases, Chongqing Municipal Key Laboratory of Oral Biomedical Engineering of Higher Education, Chongqing 401147, ChinaCollege of Stomatology, Chongqing Medical University, Chongqing Key Laboratory of Oral Diseases, Chongqing Municipal Key Laboratory of Oral Biomedical Engineering of Higher Education, Chongqing 401147, ChinaCollege of Stomatology, Chongqing Medical University, Chongqing Key Laboratory of Oral Diseases, Chongqing Municipal Key Laboratory of Oral Biomedical Engineering of Higher Education, Chongqing 401147, ChinaCollege of Stomatology, Chongqing Medical University, Chongqing Key Laboratory of Oral Diseases, Chongqing Municipal Key Laboratory of Oral Biomedical Engineering of Higher Education, Chongqing 401147, ChinaCollege of Stomatology, Chongqing Medical University, Chongqing Key Laboratory of Oral Diseases, Chongqing Municipal Key Laboratory of Oral Biomedical Engineering of Higher Education, Chongqing 401147, ChinaCollege of Stomatology, Chongqing Medical University, Chongqing Key Laboratory of Oral Diseases, Chongqing Municipal Key Laboratory of Oral Biomedical Engineering of Higher Education, Chongqing 401147, ChinaCollege of Stomatology, Chongqing Medical University, Chongqing Key Laboratory of Oral Diseases, Chongqing Municipal Key Laboratory of Oral Biomedical Engineering of Higher Education, Chongqing 401147, ChinaCorresponding author.; College of Stomatology, Chongqing Medical University, Chongqing Key Laboratory of Oral Diseases, Chongqing Municipal Key Laboratory of Oral Biomedical Engineering of Higher Education, Chongqing 401147, ChinaCorresponding author.; College of Stomatology, Chongqing Medical University, Chongqing Key Laboratory of Oral Diseases, Chongqing Municipal Key Laboratory of Oral Biomedical Engineering of Higher Education, Chongqing 401147, ChinaOrthodontic tooth movement (OTM) depends on periodontal ligament cells (PDLCs), which sense biomechanical stimuli and initiate alveolar bone remodeling. Light (optimal) forces accelerate OTM, whereas heavy forces decelerate it. However, the mechanisms by which PDLCs sense biomechanical stimuli and affect osteoclastic activities under different mechanical forces (MFs) remain unclear. This study demonstrates that mechanosensitive ion channel Piezo1-mediated Ca2+ signal conversion is crucial for sensing and delivering biomechanical signals in PDLCs under heavy-force conditions. Heavy MF up-regulated Piezo1 in PDLCs, reducing mitochondrial Ca2+ influx by inhibiting ITPR3 expression in mitochondria-associated membranes. Decreased mitochondrial calcium uptake led to reduced cytoplasmic release of mitochondrial DNA and inhibited the activation of the cGAS‒STING signaling cascade, subsequently inhibiting monocyte-to-osteoclast differentiation. Inhibition of Piezo1 or up-regulation of STING expression under heavy MF conditions significantly increased osteoclast activity and accelerated OTM. These findings suggest that heavy MF-induced Piezo1 expression in PDLCs is closely related to the control of osteoclast activity during OTM and plays an essential role in alveolar bone remodeling. This mechanism may be a potential therapeutic target for accelerating OTM.http://www.sciencedirect.com/science/article/pii/S2352304224002319BiomechanicsBone remodeling/regenerationMechanotransductionOrthodontic tooth movementPeriodontal ligament |
| spellingShingle | Ye Zhu Xuehuan Meng Qiming Zhai Liangjing Xin Hao Tan Xinyi He Xiang Li Guoyin Yang Jinlin Song Leilei Zheng Heavy mechanical force decelerates orthodontic tooth movement via Piezo1-induced mitochondrial calcium down-regulation Genes and Diseases Biomechanics Bone remodeling/regeneration Mechanotransduction Orthodontic tooth movement Periodontal ligament |
| title | Heavy mechanical force decelerates orthodontic tooth movement via Piezo1-induced mitochondrial calcium down-regulation |
| title_full | Heavy mechanical force decelerates orthodontic tooth movement via Piezo1-induced mitochondrial calcium down-regulation |
| title_fullStr | Heavy mechanical force decelerates orthodontic tooth movement via Piezo1-induced mitochondrial calcium down-regulation |
| title_full_unstemmed | Heavy mechanical force decelerates orthodontic tooth movement via Piezo1-induced mitochondrial calcium down-regulation |
| title_short | Heavy mechanical force decelerates orthodontic tooth movement via Piezo1-induced mitochondrial calcium down-regulation |
| title_sort | heavy mechanical force decelerates orthodontic tooth movement via piezo1 induced mitochondrial calcium down regulation |
| topic | Biomechanics Bone remodeling/regeneration Mechanotransduction Orthodontic tooth movement Periodontal ligament |
| url | http://www.sciencedirect.com/science/article/pii/S2352304224002319 |
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