Periodontal ligament cells under mechanical force regulate local immune homeostasis by modulating Th17/Treg cell differentiation

Objectives Improper orthodontic force often causes root resorption or destructive bone resorption. There is evidence that T helper 17 (Th17) cells and regulatory T (Treg) cells may be actively involved in bone remodeling during tooth movement. In a combination of in vitro and in vivo studies, we inv...

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Veröffentlicht in:Clinical oral investigations 2022-04, Vol.26 (4), p.3747-3764
Hauptverfasser: Lin, Jiayu, Huang, Jiachang, Zhang, Zhaoqiang, Yu, Xinyi, Cai, Xuepei, Liu, Chufeng
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container_issue 4
container_start_page 3747
container_title Clinical oral investigations
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creator Lin, Jiayu
Huang, Jiachang
Zhang, Zhaoqiang
Yu, Xinyi
Cai, Xuepei
Liu, Chufeng
description Objectives Improper orthodontic force often causes root resorption or destructive bone resorption. There is evidence that T helper 17 (Th17) cells and regulatory T (Treg) cells may be actively involved in bone remodeling during tooth movement. In a combination of in vitro and in vivo studies, we investigated the effect of human periodontal ligament cells (hPDLCs) on Th17/Treg cells under different orthodontic forces and corticotomy. Material and methods hPDLCs were cultured in vitro and subjected to different mechanical forces. The expression of interleukin (IL)-6 and transforming growth factor (TGF)-β in the supernatant and the mRNA levels of hypoxia inducible factor (HIF)-1α, Notch1, and TGF-β in hPDLCs were investigated. Supernatants were collected and co-cultured with activated CD4 + T cells, and the differentiation of Th17/Treg cells was analyzed by flow cytometry. We also established an animal model of tooth movement with or without corticotomy. The tooth movement distance, alveolar bone height, and root resorption were analyzed using micro-computed tomography. Expression of interleukin (IL)-17A, forkhead Box P3 (Foxp3), and IL-6 were analyzed using immunohistochemistry, while osteoclasts were evaluated by tartrate-resistant acid phosphatase (TRAP) staining. The mRNA levels of IL-17A, IL-6, Foxp3, IL-10, HIF-1α, notch1, and C-X-C motif chemokine ligand 12 (CXCL12) in alveolar bone and gingiva were investigated. Results Heavy force repressed cell viability and increased the mortality rate of hPDLCs; it also improved the expression of IL-6, declined the expression of TGF-β, and promoted the mRNA expression level of HIF-1α. The expression of TGF-β and Notch1 mRNA decreased and then increased. The supernatant of hPDLCs under heavy force promotes the polarization of Th17 cells. The heavy force caused root resorption and decreased alveolar bone height and increased the positive area of IL-17A immunohistochemical staining and the expression of IL-17A, IL-6, HIF-1α, and Notch1 mRNA. Corticotomy accelerated tooth movement, increased the proportion of Foxp3-positive cells, and up-regulated the expression of Foxp3, IL-10, and CXCL12 mRNA. Conclusions During orthodontic tooth movement, the heavy force causes root resorption and inflammatory bone destruction, which could be associated with increased expression of Th17 cells and IL-6. Corticotomy can accelerate tooth movement without causing root resorption and periodontal bone loss, which may be related to the in
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There is evidence that T helper 17 (Th17) cells and regulatory T (Treg) cells may be actively involved in bone remodeling during tooth movement. In a combination of in vitro and in vivo studies, we investigated the effect of human periodontal ligament cells (hPDLCs) on Th17/Treg cells under different orthodontic forces and corticotomy. Material and methods hPDLCs were cultured in vitro and subjected to different mechanical forces. The expression of interleukin (IL)-6 and transforming growth factor (TGF)-β in the supernatant and the mRNA levels of hypoxia inducible factor (HIF)-1α, Notch1, and TGF-β in hPDLCs were investigated. Supernatants were collected and co-cultured with activated CD4 + T cells, and the differentiation of Th17/Treg cells was analyzed by flow cytometry. We also established an animal model of tooth movement with or without corticotomy. The tooth movement distance, alveolar bone height, and root resorption were analyzed using micro-computed tomography. Expression of interleukin (IL)-17A, forkhead Box P3 (Foxp3), and IL-6 were analyzed using immunohistochemistry, while osteoclasts were evaluated by tartrate-resistant acid phosphatase (TRAP) staining. The mRNA levels of IL-17A, IL-6, Foxp3, IL-10, HIF-1α, notch1, and C-X-C motif chemokine ligand 12 (CXCL12) in alveolar bone and gingiva were investigated. Results Heavy force repressed cell viability and increased the mortality rate of hPDLCs; it also improved the expression of IL-6, declined the expression of TGF-β, and promoted the mRNA expression level of HIF-1α. The expression of TGF-β and Notch1 mRNA decreased and then increased. The supernatant of hPDLCs under heavy force promotes the polarization of Th17 cells. The heavy force caused root resorption and decreased alveolar bone height and increased the positive area of IL-17A immunohistochemical staining and the expression of IL-17A, IL-6, HIF-1α, and Notch1 mRNA. Corticotomy accelerated tooth movement, increased the proportion of Foxp3-positive cells, and up-regulated the expression of Foxp3, IL-10, and CXCL12 mRNA. Conclusions During orthodontic tooth movement, the heavy force causes root resorption and inflammatory bone destruction, which could be associated with increased expression of Th17 cells and IL-6. Corticotomy can accelerate tooth movement without causing root resorption and periodontal bone loss, which may be related to the increased expression of Treg cells. Clinical relevance Altogether, this report provides a new perspective on the prevention of inflammatory injury via the regulation of Th17/Treg cells in orthodontics.</description><identifier>ISSN: 1436-3771</identifier><identifier>ISSN: 1432-6981</identifier><identifier>EISSN: 1436-3771</identifier><identifier>DOI: 10.1007/s00784-021-04346-0</identifier><identifier>PMID: 35029749</identifier><language>eng</language><publisher>Berlin/Heidelberg: Springer Berlin Heidelberg</publisher><subject>Acid phosphatase (tartrate-resistant) ; Alveolar bone ; Animal models ; Bone loss ; Bone remodeling ; Bone resorption ; CD4 antigen ; Cell differentiation ; Chemokines ; Computed tomography ; CXCL12 protein ; Cytokines ; Dentistry ; Flow cytometry ; Forkhead protein ; Foxp3 protein ; Gene expression ; Helper cells ; Homeostasis ; Hypoxia-inducible factor 1a ; Immunohistochemistry ; Inflammation ; Interleukin 10 ; Interleukin 6 ; Ligaments ; Lymphocytes T ; Medicine ; Notch1 protein ; Original Article ; Orthodontics ; Root resorption ; Teeth ; Transforming growth factor-b</subject><ispartof>Clinical oral investigations, 2022-04, Vol.26 (4), p.3747-3764</ispartof><rights>The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature 2022</rights><rights>2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.</rights><rights>The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature 2022.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c375t-57e78c905b42c4d473d21e66666cee22cd92c157a69ed375289ffe40384612fb3</citedby><cites>FETCH-LOGICAL-c375t-57e78c905b42c4d473d21e66666cee22cd92c157a69ed375289ffe40384612fb3</cites><orcidid>0000-0002-3995-0148</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s00784-021-04346-0$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s00784-021-04346-0$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,780,784,27915,27916,41479,42548,51310</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/35029749$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Lin, Jiayu</creatorcontrib><creatorcontrib>Huang, Jiachang</creatorcontrib><creatorcontrib>Zhang, Zhaoqiang</creatorcontrib><creatorcontrib>Yu, Xinyi</creatorcontrib><creatorcontrib>Cai, Xuepei</creatorcontrib><creatorcontrib>Liu, Chufeng</creatorcontrib><title>Periodontal ligament cells under mechanical force regulate local immune homeostasis by modulating Th17/Treg cell differentiation</title><title>Clinical oral investigations</title><addtitle>Clin Oral Invest</addtitle><addtitle>Clin Oral Investig</addtitle><description>Objectives Improper orthodontic force often causes root resorption or destructive bone resorption. There is evidence that T helper 17 (Th17) cells and regulatory T (Treg) cells may be actively involved in bone remodeling during tooth movement. In a combination of in vitro and in vivo studies, we investigated the effect of human periodontal ligament cells (hPDLCs) on Th17/Treg cells under different orthodontic forces and corticotomy. Material and methods hPDLCs were cultured in vitro and subjected to different mechanical forces. The expression of interleukin (IL)-6 and transforming growth factor (TGF)-β in the supernatant and the mRNA levels of hypoxia inducible factor (HIF)-1α, Notch1, and TGF-β in hPDLCs were investigated. Supernatants were collected and co-cultured with activated CD4 + T cells, and the differentiation of Th17/Treg cells was analyzed by flow cytometry. We also established an animal model of tooth movement with or without corticotomy. The tooth movement distance, alveolar bone height, and root resorption were analyzed using micro-computed tomography. Expression of interleukin (IL)-17A, forkhead Box P3 (Foxp3), and IL-6 were analyzed using immunohistochemistry, while osteoclasts were evaluated by tartrate-resistant acid phosphatase (TRAP) staining. The mRNA levels of IL-17A, IL-6, Foxp3, IL-10, HIF-1α, notch1, and C-X-C motif chemokine ligand 12 (CXCL12) in alveolar bone and gingiva were investigated. Results Heavy force repressed cell viability and increased the mortality rate of hPDLCs; it also improved the expression of IL-6, declined the expression of TGF-β, and promoted the mRNA expression level of HIF-1α. The expression of TGF-β and Notch1 mRNA decreased and then increased. The supernatant of hPDLCs under heavy force promotes the polarization of Th17 cells. The heavy force caused root resorption and decreased alveolar bone height and increased the positive area of IL-17A immunohistochemical staining and the expression of IL-17A, IL-6, HIF-1α, and Notch1 mRNA. Corticotomy accelerated tooth movement, increased the proportion of Foxp3-positive cells, and up-regulated the expression of Foxp3, IL-10, and CXCL12 mRNA. Conclusions During orthodontic tooth movement, the heavy force causes root resorption and inflammatory bone destruction, which could be associated with increased expression of Th17 cells and IL-6. Corticotomy can accelerate tooth movement without causing root resorption and periodontal bone loss, which may be related to the increased expression of Treg cells. 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Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health &amp; Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Biological Science Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>MEDLINE - Academic</collection><jtitle>Clinical oral investigations</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Lin, Jiayu</au><au>Huang, Jiachang</au><au>Zhang, Zhaoqiang</au><au>Yu, Xinyi</au><au>Cai, Xuepei</au><au>Liu, Chufeng</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Periodontal ligament cells under mechanical force regulate local immune homeostasis by modulating Th17/Treg cell differentiation</atitle><jtitle>Clinical oral investigations</jtitle><stitle>Clin Oral Invest</stitle><addtitle>Clin Oral Investig</addtitle><date>2022-04-01</date><risdate>2022</risdate><volume>26</volume><issue>4</issue><spage>3747</spage><epage>3764</epage><pages>3747-3764</pages><issn>1436-3771</issn><issn>1432-6981</issn><eissn>1436-3771</eissn><abstract>Objectives Improper orthodontic force often causes root resorption or destructive bone resorption. There is evidence that T helper 17 (Th17) cells and regulatory T (Treg) cells may be actively involved in bone remodeling during tooth movement. In a combination of in vitro and in vivo studies, we investigated the effect of human periodontal ligament cells (hPDLCs) on Th17/Treg cells under different orthodontic forces and corticotomy. Material and methods hPDLCs were cultured in vitro and subjected to different mechanical forces. The expression of interleukin (IL)-6 and transforming growth factor (TGF)-β in the supernatant and the mRNA levels of hypoxia inducible factor (HIF)-1α, Notch1, and TGF-β in hPDLCs were investigated. Supernatants were collected and co-cultured with activated CD4 + T cells, and the differentiation of Th17/Treg cells was analyzed by flow cytometry. We also established an animal model of tooth movement with or without corticotomy. The tooth movement distance, alveolar bone height, and root resorption were analyzed using micro-computed tomography. Expression of interleukin (IL)-17A, forkhead Box P3 (Foxp3), and IL-6 were analyzed using immunohistochemistry, while osteoclasts were evaluated by tartrate-resistant acid phosphatase (TRAP) staining. The mRNA levels of IL-17A, IL-6, Foxp3, IL-10, HIF-1α, notch1, and C-X-C motif chemokine ligand 12 (CXCL12) in alveolar bone and gingiva were investigated. Results Heavy force repressed cell viability and increased the mortality rate of hPDLCs; it also improved the expression of IL-6, declined the expression of TGF-β, and promoted the mRNA expression level of HIF-1α. The expression of TGF-β and Notch1 mRNA decreased and then increased. The supernatant of hPDLCs under heavy force promotes the polarization of Th17 cells. The heavy force caused root resorption and decreased alveolar bone height and increased the positive area of IL-17A immunohistochemical staining and the expression of IL-17A, IL-6, HIF-1α, and Notch1 mRNA. Corticotomy accelerated tooth movement, increased the proportion of Foxp3-positive cells, and up-regulated the expression of Foxp3, IL-10, and CXCL12 mRNA. Conclusions During orthodontic tooth movement, the heavy force causes root resorption and inflammatory bone destruction, which could be associated with increased expression of Th17 cells and IL-6. Corticotomy can accelerate tooth movement without causing root resorption and periodontal bone loss, which may be related to the increased expression of Treg cells. Clinical relevance Altogether, this report provides a new perspective on the prevention of inflammatory injury via the regulation of Th17/Treg cells in orthodontics.</abstract><cop>Berlin/Heidelberg</cop><pub>Springer Berlin Heidelberg</pub><pmid>35029749</pmid><doi>10.1007/s00784-021-04346-0</doi><tpages>18</tpages><orcidid>https://orcid.org/0000-0002-3995-0148</orcidid></addata></record>
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subjects Acid phosphatase (tartrate-resistant)
Alveolar bone
Animal models
Bone loss
Bone remodeling
Bone resorption
CD4 antigen
Cell differentiation
Chemokines
Computed tomography
CXCL12 protein
Cytokines
Dentistry
Flow cytometry
Forkhead protein
Foxp3 protein
Gene expression
Helper cells
Homeostasis
Hypoxia-inducible factor 1a
Immunohistochemistry
Inflammation
Interleukin 10
Interleukin 6
Ligaments
Lymphocytes T
Medicine
Notch1 protein
Original Article
Orthodontics
Root resorption
Teeth
Transforming growth factor-b
title Periodontal ligament cells under mechanical force regulate local immune homeostasis by modulating Th17/Treg cell differentiation
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