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Tensile force-induced PDGF-BB/PDGFRβ signals in periodontal ligament fibroblasts activate JAK2/STAT3 for orthodontic tooth movement

Orthodontic force-induced osteogenic differentiation and bone formation at tension side play a pivotal role in orthodontic tooth movement (OTM). Platelet-derived growth factor-BB (PDGF-BB) is a clinically proven growth factor during bone regeneration process with unclear mechanisms. Fibroblasts in p...

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Autores principales: Jin, Yuqin, Ding, Liang, Ding, Zhuang, Fu, Yong, Song, Yuxian, Jing, Yue, Li, Qiang, Zhang, Jianyun, Ni, Yanhong, Hu, Qingang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7347599/
https://www.ncbi.nlm.nih.gov/pubmed/32647179
http://dx.doi.org/10.1038/s41598-020-68068-1
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author Jin, Yuqin
Ding, Liang
Ding, Zhuang
Fu, Yong
Song, Yuxian
Jing, Yue
Li, Qiang
Zhang, Jianyun
Ni, Yanhong
Hu, Qingang
author_facet Jin, Yuqin
Ding, Liang
Ding, Zhuang
Fu, Yong
Song, Yuxian
Jing, Yue
Li, Qiang
Zhang, Jianyun
Ni, Yanhong
Hu, Qingang
author_sort Jin, Yuqin
collection PubMed
description Orthodontic force-induced osteogenic differentiation and bone formation at tension side play a pivotal role in orthodontic tooth movement (OTM). Platelet-derived growth factor-BB (PDGF-BB) is a clinically proven growth factor during bone regeneration process with unclear mechanisms. Fibroblasts in periodontal ligament (PDL) are considered to be mechanosensitive under orthodontic force. Thus, we established OTM model to investigate the correlation between PDGF-BB and fibroblasts during bone regeneration at tension side. We confirmed that tensile force stimulated PDL cells to induce osteogenic differentiation via Runx-2, OCN up-regulation, and to accelerate new bone deposition along the periodontium and the alveolar bone interface. Interestingly, PDGF-BB level was remarkably enhanced at tension side during OTM in parallel with up-regulated PDGFRβ+/α-SMA+ fibroblasts in PDL by immunohistochemistry. Moreover, orthodontic force-treated primary fibroblasts from PDL were isolated and, cultured in vitro, which showed similar morphology and phenotype with control fibroblasts without OTM treatment. PDGFRβ expression was confirmed to be increased in orthodontic force-treated fibroblasts by immunofluorescence and flow cytometry. Bioinformatics analysis identified that PDGF-BB/PDGFRβ signals were relevant to the activation of JAK/STAT3 signals. The protein expression of JAK2 and STAT3 was elevated in PDL of tension side. Importantly, in vivo, the treatment of the inhibitors (imatinib and AG490) for PDGFRβ and JAK–STAT signals were capable of attenuating the tooth movement. The osteogenic differentiation and bone regeneration in tension side were down-regulated upon the treatment of inhibitors during OTM. Meanwhile, the expressions of PDGFRβ, JAK2 and STAT3 were inhibited by imatinib and AG490. Thus, we concluded that tensile force-induced PDGF-BB activated JAK2/STAT3 signals in PDGFRβ(+) fibroblasts in bone formation during OTM.
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spelling pubmed-73475992020-07-10 Tensile force-induced PDGF-BB/PDGFRβ signals in periodontal ligament fibroblasts activate JAK2/STAT3 for orthodontic tooth movement Jin, Yuqin Ding, Liang Ding, Zhuang Fu, Yong Song, Yuxian Jing, Yue Li, Qiang Zhang, Jianyun Ni, Yanhong Hu, Qingang Sci Rep Article Orthodontic force-induced osteogenic differentiation and bone formation at tension side play a pivotal role in orthodontic tooth movement (OTM). Platelet-derived growth factor-BB (PDGF-BB) is a clinically proven growth factor during bone regeneration process with unclear mechanisms. Fibroblasts in periodontal ligament (PDL) are considered to be mechanosensitive under orthodontic force. Thus, we established OTM model to investigate the correlation between PDGF-BB and fibroblasts during bone regeneration at tension side. We confirmed that tensile force stimulated PDL cells to induce osteogenic differentiation via Runx-2, OCN up-regulation, and to accelerate new bone deposition along the periodontium and the alveolar bone interface. Interestingly, PDGF-BB level was remarkably enhanced at tension side during OTM in parallel with up-regulated PDGFRβ+/α-SMA+ fibroblasts in PDL by immunohistochemistry. Moreover, orthodontic force-treated primary fibroblasts from PDL were isolated and, cultured in vitro, which showed similar morphology and phenotype with control fibroblasts without OTM treatment. PDGFRβ expression was confirmed to be increased in orthodontic force-treated fibroblasts by immunofluorescence and flow cytometry. Bioinformatics analysis identified that PDGF-BB/PDGFRβ signals were relevant to the activation of JAK/STAT3 signals. The protein expression of JAK2 and STAT3 was elevated in PDL of tension side. Importantly, in vivo, the treatment of the inhibitors (imatinib and AG490) for PDGFRβ and JAK–STAT signals were capable of attenuating the tooth movement. The osteogenic differentiation and bone regeneration in tension side were down-regulated upon the treatment of inhibitors during OTM. Meanwhile, the expressions of PDGFRβ, JAK2 and STAT3 were inhibited by imatinib and AG490. Thus, we concluded that tensile force-induced PDGF-BB activated JAK2/STAT3 signals in PDGFRβ(+) fibroblasts in bone formation during OTM. Nature Publishing Group UK 2020-07-09 /pmc/articles/PMC7347599/ /pubmed/32647179 http://dx.doi.org/10.1038/s41598-020-68068-1 Text en © The Author(s) 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Jin, Yuqin
Ding, Liang
Ding, Zhuang
Fu, Yong
Song, Yuxian
Jing, Yue
Li, Qiang
Zhang, Jianyun
Ni, Yanhong
Hu, Qingang
Tensile force-induced PDGF-BB/PDGFRβ signals in periodontal ligament fibroblasts activate JAK2/STAT3 for orthodontic tooth movement
title Tensile force-induced PDGF-BB/PDGFRβ signals in periodontal ligament fibroblasts activate JAK2/STAT3 for orthodontic tooth movement
title_full Tensile force-induced PDGF-BB/PDGFRβ signals in periodontal ligament fibroblasts activate JAK2/STAT3 for orthodontic tooth movement
title_fullStr Tensile force-induced PDGF-BB/PDGFRβ signals in periodontal ligament fibroblasts activate JAK2/STAT3 for orthodontic tooth movement
title_full_unstemmed Tensile force-induced PDGF-BB/PDGFRβ signals in periodontal ligament fibroblasts activate JAK2/STAT3 for orthodontic tooth movement
title_short Tensile force-induced PDGF-BB/PDGFRβ signals in periodontal ligament fibroblasts activate JAK2/STAT3 for orthodontic tooth movement
title_sort tensile force-induced pdgf-bb/pdgfrβ signals in periodontal ligament fibroblasts activate jak2/stat3 for orthodontic tooth movement
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7347599/
https://www.ncbi.nlm.nih.gov/pubmed/32647179
http://dx.doi.org/10.1038/s41598-020-68068-1
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