Force-induced Caspase-1-dependent pyroptosis regulates orthodontic tooth movement.

IF 10.8 1区 医学 Q1 DENTISTRY, ORAL SURGERY & MEDICINE International Journal of Oral Science Pub Date : 2024-01-15 DOI:10.1038/s41368-023-00268-7
Liyuan Chen, Huajie Yu, Zixin Li, Yu Wang, Shanshan Jin, Min Yu, Lisha Zhu, Chengye Ding, Xiaolan Wu, Tianhao Wu, Chunlei Xun, Yanheng Zhou, Danqing He, Yan Liu
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Abstract

Pyroptosis, an inflammatory caspase-dependent programmed cell death, plays a vital role in maintaining tissue homeostasis and activating inflammatory responses. Orthodontic tooth movement (OTM) is an aseptic force-induced inflammatory bone remodeling process mediated by the activation of periodontal ligament (PDL) progenitor cells. However, whether and how force induces PDL progenitor cell pyroptosis, thereby influencing OTM and alveolar bone remodeling remains unknown. In this study, we found that mechanical force induced the expression of pyroptosis-related markers in rat OTM and alveolar bone remodeling process. Blocking or enhancing pyroptosis level could suppress or promote OTM and alveolar bone remodeling respectively. Using Caspase-1-/- mice, we further demonstrated that the functional role of the force-induced pyroptosis in PDL progenitor cells depended on Caspase-1. Moreover, mechanical force could also induce pyroptosis in human ex-vivo force-treated PDL progenitor cells and in compressive force-loaded PDL progenitor cells in vitro, which influenced osteoclastogenesis. Mechanistically, transient receptor potential subfamily V member 4 signaling was involved in force-induced Caspase-1-dependent pyroptosis in PDL progenitor cells. Overall, this study suggested a novel mechanism contributing to the modulation of osteoclastogenesis and alveolar bone remodeling under mechanical stimuli, indicating a promising approach to accelerate OTM by targeting Caspase-1.

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力诱导的 Caspase-1 依赖性裂解调节正畸牙齿的移动。
裂解是一种依赖于炎性卡巴酶的程序性细胞死亡,在维持组织稳态和激活炎症反应方面发挥着重要作用。正畸牙齿移动(OTM)是一种无菌力诱导的炎性骨重塑过程,由牙周韧带(PDL)祖细胞激活介导。然而,外力是否以及如何诱导牙周韧带祖细胞热解,从而影响 OTM 和牙槽骨重塑仍是未知数。在这项研究中,我们发现机械力能诱导大鼠 OTM 和牙槽骨重塑过程中热凋亡相关标志物的表达。阻断或提高热凋亡水平可分别抑制或促进 OTM 和牙槽骨重塑。利用Caspase-1-/-小鼠,我们进一步证实了PDL祖细胞受力诱导的热凋亡的功能作用依赖于Caspase-1。此外,机械力还能诱导人体内外力处理的PDL祖细胞和体外压缩力加载的PDL祖细胞发生热凋亡,从而影响破骨细胞的生成。从机理上讲,瞬时受体电位亚家族 V 成员 4 信号转导参与了力诱导的 Caspase-1 依赖性 PDL 祖细胞的破骨细胞生成。总之,这项研究提出了一种在机械刺激下调节破骨细胞生成和牙槽骨重塑的新机制,为通过靶向Caspase-1加速OTM提供了一种可行的方法。
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来源期刊
International Journal of Oral Science
International Journal of Oral Science DENTISTRY, ORAL SURGERY & MEDICINE-
CiteScore
31.80
自引率
1.30%
发文量
53
审稿时长
>12 weeks
期刊介绍: The International Journal of Oral Science covers various aspects of oral science and interdisciplinary fields, encompassing basic, applied, and clinical research. Topics include, but are not limited to: Oral microbiology Oral and maxillofacial oncology Cariology Oral inflammation and infection Dental stem cells and regenerative medicine Craniofacial surgery Dental material Oral biomechanics Oral, dental, and maxillofacial genetic and developmental diseases Craniofacial bone research Craniofacial-related biomaterials Temporomandibular joint disorder and osteoarthritis The journal publishes peer-reviewed Articles presenting new research results and Review Articles offering concise summaries of specific areas in oral science.
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