Orthodontic Compression Enhances Macrophage M2 Polarization via Histone H3 Hyperacetylation

Orthodontic tooth movement is a complex periodontal remodeling process triggered by compression that involves sterile inflammation and immune responses. Macrophages are mechanically sensitive immune cells, but their role in orthodontic tooth movement is unclear. Here, we hypothesize that orthodontic...

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Main Authors: Yao Wang, Sabine Groeger, Jiawen Yong, Sabine Ruf
Format: Article
Language:English
Published: MDPI AG 2023-02-01
Series:International Journal of Molecular Sciences
Subjects:
Online Access:https://www.mdpi.com/1422-0067/24/4/3117
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author Yao Wang
Sabine Groeger
Jiawen Yong
Sabine Ruf
author_facet Yao Wang
Sabine Groeger
Jiawen Yong
Sabine Ruf
author_sort Yao Wang
collection DOAJ
description Orthodontic tooth movement is a complex periodontal remodeling process triggered by compression that involves sterile inflammation and immune responses. Macrophages are mechanically sensitive immune cells, but their role in orthodontic tooth movement is unclear. Here, we hypothesize that orthodontic force can activate macrophages, and their activation may be associated with orthodontic root resorption. After force-loading and/or adiponectin application, the migration function of macrophages was tested via scratch assay, and <i>Nos2</i>, <i>Il1b</i>, <i>Arg1</i>, <i>Il10</i>, <i>ApoE</i>, and <i>Saa3</i> expression levels were detected using qRT-PCR. Furthermore, H3 histone acetylation was measured using an acetylation detection kit. The specific inhibitor of H3 histone, I-BET762, was deployed to observe its effect on macrophages. In addition, cementoblasts were treated with macrophage-conditioned medium or compression force, and OPG production and cellular migration were measured. We further detected Piezo1 expression in cementoblasts via qRT-PCR and Western-blot, and its effect on the force-induced impairment of cementoblastic functions was also analyzed. Compressive force significantly inhibited macrophage migration. <i>Nos2</i> was up-regulated 6 h after force-loading. <i>Il1b</i>, <i>Arg1</i>, <i>Il10</i>, <i>Saa3</i>, and <i>ApoE</i> increased after 24 h. Meanwhile, higher H3 histone acetylation was detected in the macrophages subjected to compression, and I-BET762 dampened the expression of M2 polarization markers (<i>Arg1</i> and <i>Il10</i>). Lastly, even though the activated macrophage-conditioned medium showed no effect on cementoblasts, compressive force directly impaired cementoblastic function by enhancing mechanoreceptor Piezo1. Compressive force activates macrophages; specifically, it causes M2 polarization via H3 histone acetylation in the late stage. Compression-induced orthodontic root resorption is macrophage-independent, but it involves the activation of mechanoreceptor Piezo1.
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spelling doaj.art-2601abf17e9945f08bc27de34256eb122023-11-16T20:55:33ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-02-01244311710.3390/ijms24043117Orthodontic Compression Enhances Macrophage M2 Polarization via Histone H3 HyperacetylationYao Wang0Sabine Groeger1Jiawen Yong2Sabine Ruf3Department of Orthodontics, Faculty of Medicine, Justus Liebig University Giessen, 35392 Giessen, GermanyDepartment of Orthodontics, Faculty of Medicine, Justus Liebig University Giessen, 35392 Giessen, GermanyDepartment of Orthodontics, Faculty of Medicine, Justus Liebig University Giessen, 35392 Giessen, GermanyDepartment of Orthodontics, Faculty of Medicine, Justus Liebig University Giessen, 35392 Giessen, GermanyOrthodontic tooth movement is a complex periodontal remodeling process triggered by compression that involves sterile inflammation and immune responses. Macrophages are mechanically sensitive immune cells, but their role in orthodontic tooth movement is unclear. Here, we hypothesize that orthodontic force can activate macrophages, and their activation may be associated with orthodontic root resorption. After force-loading and/or adiponectin application, the migration function of macrophages was tested via scratch assay, and <i>Nos2</i>, <i>Il1b</i>, <i>Arg1</i>, <i>Il10</i>, <i>ApoE</i>, and <i>Saa3</i> expression levels were detected using qRT-PCR. Furthermore, H3 histone acetylation was measured using an acetylation detection kit. The specific inhibitor of H3 histone, I-BET762, was deployed to observe its effect on macrophages. In addition, cementoblasts were treated with macrophage-conditioned medium or compression force, and OPG production and cellular migration were measured. We further detected Piezo1 expression in cementoblasts via qRT-PCR and Western-blot, and its effect on the force-induced impairment of cementoblastic functions was also analyzed. Compressive force significantly inhibited macrophage migration. <i>Nos2</i> was up-regulated 6 h after force-loading. <i>Il1b</i>, <i>Arg1</i>, <i>Il10</i>, <i>Saa3</i>, and <i>ApoE</i> increased after 24 h. Meanwhile, higher H3 histone acetylation was detected in the macrophages subjected to compression, and I-BET762 dampened the expression of M2 polarization markers (<i>Arg1</i> and <i>Il10</i>). Lastly, even though the activated macrophage-conditioned medium showed no effect on cementoblasts, compressive force directly impaired cementoblastic function by enhancing mechanoreceptor Piezo1. Compressive force activates macrophages; specifically, it causes M2 polarization via H3 histone acetylation in the late stage. Compression-induced orthodontic root resorption is macrophage-independent, but it involves the activation of mechanoreceptor Piezo1.https://www.mdpi.com/1422-0067/24/4/3117compressive forcemacrophagespolarizationH3 histoneacetylationadiponectin
spellingShingle Yao Wang
Sabine Groeger
Jiawen Yong
Sabine Ruf
Orthodontic Compression Enhances Macrophage M2 Polarization via Histone H3 Hyperacetylation
International Journal of Molecular Sciences
compressive force
macrophages
polarization
H3 histone
acetylation
adiponectin
title Orthodontic Compression Enhances Macrophage M2 Polarization via Histone H3 Hyperacetylation
title_full Orthodontic Compression Enhances Macrophage M2 Polarization via Histone H3 Hyperacetylation
title_fullStr Orthodontic Compression Enhances Macrophage M2 Polarization via Histone H3 Hyperacetylation
title_full_unstemmed Orthodontic Compression Enhances Macrophage M2 Polarization via Histone H3 Hyperacetylation
title_short Orthodontic Compression Enhances Macrophage M2 Polarization via Histone H3 Hyperacetylation
title_sort orthodontic compression enhances macrophage m2 polarization via histone h3 hyperacetylation
topic compressive force
macrophages
polarization
H3 histone
acetylation
adiponectin
url https://www.mdpi.com/1422-0067/24/4/3117
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AT sabinegroeger orthodonticcompressionenhancesmacrophagem2polarizationviahistoneh3hyperacetylation
AT jiawenyong orthodonticcompressionenhancesmacrophagem2polarizationviahistoneh3hyperacetylation
AT sabineruf orthodonticcompressionenhancesmacrophagem2polarizationviahistoneh3hyperacetylation