Ubiquitin C-terminal hydrolase L1 activation in periodontal ligament cells mediates orthodontic tooth movement via the MAPK signaling pathway.

IF 2.8 4区医学 Q3 CELL BIOLOGY Connective Tissue Research Pub Date : 2024-09-02 DOI:10.1080/03008207.2024.2395998

Fu Zheng, Feifei Wang, Tong Wu, Hongyi Tang, Huazhi Li, Xinyu Cui, Cuiying Li, Jiuhui Jiang

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Abstract

Purpose: Periodontal ligament cells (PDLCs) play a significant role in orthodontic force induced bone remodeling. However, the molecular mechanisms by which PDLCs respond to mechanical stimuli and influence osteoclastic activities remain unclear. This study aims to investigate the role of UCHL1, a key deubiquitinating enzyme involved in protein degradation and cellular responses, in force-treated PDLCs during orthodontic tooth movement (OTM).

Materials and methods: In this study, we conducted in vivo and in vitro experiments using human PDLCs and a rat model of OTM. Mechanical stress was applied to PDLCs, and UCHL1 expression was analyzed through quantitative real-time polymerase chain reaction (qPCR), Western blot, and immunofluorescence staining. UCHL1 knockdown was achieved using siRNA, and its effects on osteoclast differentiation were assessed. The role of the MAPK/ERK pathway was investigated using the MEK-specific inhibitor U0126. An animal model of OTM was established, and the impact of UCHL1 inhibitor-LDN57444 on OTM and osteoclastic activity was evaluated through micro-CT analysis, histological staining, and immunohistochemistry.

Results: Mechanical force induced UCHL1 expression in PDLCs during OTM. UCHL1 knockdown downregulated the RANKL/OPG ratio in PDLCs, affecting osteoclast differentiation. LDN57444 inhibited OTM and osteoclastic activity. UCHL1 activation correlated with ERK1/2 phosphorylation in force-treated PDLCs.

Conclusions: Mechanical force mediated UCHL1 activation in PDLCs promotes osteoclast differentiation via the ERK1/2 signaling pathway during OTM.

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牙周韧带细胞中泛素 C 端水解酶 L1 的激活通过 MAPK 信号通路介导正畸牙齿移动。

目的：牙周韧带细胞（PDLCs）在正畸力诱导的骨重塑中发挥着重要作用。然而，牙周韧带细胞对机械刺激做出反应并影响破骨细胞活动的分子机制仍不清楚。本研究旨在探讨 UCHL1（一种参与蛋白质降解和细胞反应的关键去泛素化酶）在正畸牙齿移动（OTM）过程中受力处理的 PDLCs 中的作用：在本研究中，我们使用人类 PDLCs 和 OTM 大鼠模型进行了体内和体外实验。对 PDLCs 施加机械应力，并通过实时定量聚合酶链反应（qPCR）、Western 印迹和免疫荧光染色分析 UCHL1 的表达。使用 siRNA 敲除 UCHL1，并评估其对破骨细胞分化的影响。使用 MEK 特异性抑制剂 U0126 研究了 MAPK/ERK 通路的作用。建立了 OTM 动物模型，并通过显微 CT 分析、组织学染色和免疫组化评估了 UCHL1 抑制剂-LDN57444 对 OTM 和破骨细胞活性的影响：结果：OTM过程中，机械力诱导PDLCs中UCHL1的表达。敲除 UCHL1 会降低 PDLCs 中的 RANKL/OPG 比率，从而影响破骨细胞的分化。LDN57444 可抑制 OTM 和破骨细胞活性。在受力处理的PDLCs中，UCHL1的激活与ERK1/2磷酸化相关：结论：在 OTM 过程中，机械力介导的 PDLCs 中的 UCHL1 激活可通过 ERK1/2 信号通路促进破骨细胞分化。

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来源期刊

Connective Tissue Research 生物-细胞生物学

CiteScore

6.60

自引率

3.40%

发文量

审稿时长

2 months

期刊介绍： The aim of Connective Tissue Research is to present original and significant research in all basic areas of connective tissue and matrix biology. The journal also provides topical reviews and, on occasion, the proceedings of conferences in areas of special interest at which original work is presented. The journal supports an interdisciplinary approach; we present a variety of perspectives from different disciplines, including Biochemistry Cell and Molecular Biology Immunology Structural Biology Biophysics Biomechanics Regenerative Medicine The interests of the Editorial Board are to understand, mechanistically, the structure-function relationships in connective tissue extracellular matrix, and its associated cells, through interpretation of sophisticated experimentation using state-of-the-art technologies that include molecular genetics, imaging, immunology, biomechanics and tissue engineering.