重型机械力通过 Piezo1 诱导的线粒体钙下调,使牙齿矫正运动减速

IF 6.9 2区 医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY
Ye Zhu, Xuehuan Meng, Qiming Zhai, Liangjing Xin, Hao Tan, Xinyi He, Xiang Li, Guoyin Yang, Jinlin Song, Leilei Zheng
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引用次数: 0

摘要

正畸牙齿移动(OTM)取决于牙周韧带细胞(PDLCs),它们能感知生物力学刺激并启动牙槽骨重塑。轻(最佳)力加速 OTM,而重力则使其减速。然而,PDLCs 在不同机械力(MFs)下感知生物力学刺激并影响破骨细胞活动的机制仍不清楚。本研究证明,在重力条件下,机械敏感性离子通道Piezo1介导的Ca2+信号转换是PDLCs感知和传递生物力学信号的关键。重力上调了 PDLCs 中的 Piezo1,通过抑制线粒体相关膜中 ITPR3 的表达减少了线粒体 Ca2+ 的流入。线粒体钙吸收的减少导致线粒体 DNA 胞质释放的减少,并抑制了 cGAS-STING 信号级联的激活,从而抑制了单核细胞向破骨细胞的分化。在重型 MF 条件下抑制 Piezo1 或上调 STING 的表达可显著增加破骨细胞的活性并加速 OTM。这些发现表明,重型 MF 诱导的 Piezo1 在 PDLCs 中的表达与 OTM 过程中破骨细胞活性的控制密切相关,并在牙槽骨重塑过程中发挥着重要作用。这一机制可能是加速 OTM 的潜在治疗靶点。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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 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.
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来源期刊
Genes & Diseases
Genes & Diseases Multiple-
CiteScore
7.30
自引率
0.00%
发文量
347
审稿时长
49 days
期刊介绍: Genes & Diseases is an international journal for molecular and translational medicine. The journal primarily focuses on publishing investigations on the molecular bases and experimental therapeutics of human diseases. Publication formats include full length research article, review article, short communication, correspondence, perspectives, commentary, views on news, and research watch. Aims and Scopes Genes & Diseases publishes rigorously peer-reviewed and high quality original articles and authoritative reviews that focus on the molecular bases of human diseases. Emphasis will be placed on hypothesis-driven, mechanistic studies relevant to pathogenesis and/or experimental therapeutics of human diseases. The journal has worldwide authorship, and a broad scope in basic and translational biomedical research of molecular biology, molecular genetics, and cell biology, including but not limited to cell proliferation and apoptosis, signal transduction, stem cell biology, developmental biology, gene regulation and epigenetics, cancer biology, immunity and infection, neuroscience, disease-specific animal models, gene and cell-based therapies, and regenerative medicine.
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