Gold Nanoparticles Promote the Bone Regeneration of Periodontal Ligament Stem Cell Sheets Through Activation of Autophagy

Yangheng Zhang,1,* Peng Wang,2,* Yuxian Wang,3,* Jiao Li,4 Dan Qiao,1 Rixin Chen,1 Wenrong Yang,5 Fuhua Yan1 1Department of Periodontology, Nanjing Stomatological Hospital, Medical School of Nanjing University, Nanjing, Jiangsu, People’s Republic of China; 2State Key Laboratory of Pharmace...

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Autores principales: Zhang Y, Wang P, Wang Y, Li J, Qiao D, Chen R, Yang W, Yan F
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Publicado: Dove Medical Press 2021
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spelling oai:doaj.org-article:522d8be746c744d988527768e9a0a9bc2021-12-02T13:43:20ZGold Nanoparticles Promote the Bone Regeneration of Periodontal Ligament Stem Cell Sheets Through Activation of Autophagy1178-2013https://doaj.org/article/522d8be746c744d988527768e9a0a9bc2021-01-01T00:00:00Zhttps://www.dovepress.com/gold-nanoparticles-promote-the-bone-regeneration-of-periodontal-ligame-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Yangheng Zhang,1,* Peng Wang,2,* Yuxian Wang,3,* Jiao Li,4 Dan Qiao,1 Rixin Chen,1 Wenrong Yang,5 Fuhua Yan1 1Department of Periodontology, Nanjing Stomatological Hospital, Medical School of Nanjing University, Nanjing, Jiangsu, People’s Republic of China; 2State Key Laboratory of Pharmaceutical Biotechnology, Department of Sports Medicine and Adult Reconstructive Surgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, Jiangsu, People’s Republic of China; 3College of Biotechnology and Pharmaceutical Engineering, Nanjing Tech University, Nanjing, Jiangsu, People’s Republic of China; 4Department of Orthodontics, Nanjing Stomatological Hospital, Medical School of Nanjing University, Nanjing, Jiangsu, People’s Republic of China; 5School of Life and Environmental Science, Centre for Chemistry and Biotechnology, Deakin University, Geelong, VIC, Australia*These authors contributed equally to this workCorrespondence: Fuhua YanNanjing Stomatological Hospital, Medical School of Nanjing University, 30 Zhongyang Road, Nanjing, Jiangsu 210008, People’s Republic of ChinaTel +86 25 8362 0253Fax +86 25 8362 0202Email yanfh@nju.edu.cnObjective: Cell sheet technology (CST) is advantageous for repairing alveolar bone defects in clinical situations, and osteogenic induction before implantation may result in enhanced bone regeneration. Herein, we observed the effect of gold nanoparticles (AuNPs) on osteogenic differentiation of periodontal ligament stem cell (PDLSC) sheets and explored their potential mechanism of action.Methods: PDLSCs were cultured in cell sheet induction medium to obtain cell sheets. PDLSC sheets were treated with or without AuNPs. Alkaline phosphatase, alizarin red S, von Kossa, and immunofluorescence staining were used to observe the effects of AuNPs on the osteogenic differentiation of PDLSC sheets. Western blotting was performed to evaluate the osteogenic effects and autophagy activity. The cell sheets were transplanted into the dorsa of nude mice, and bone regeneration was analyzed by micro-CT and histological staining.Results: AuNPs could promote the osteogenic differentiation of PDLSC sheets by upregulating bone-related protein expression and mineralization. The 45-nm AuNPs were more effective than 13-nm AuNPs. Additional analysis demonstrated that their ability to promote differentiation could depend on activation of the autophagy pathway through upregulation of microtubule-associated protein light chain 3 and downregulation of sequestosome 1/p62. Furthermore, AuNPs significantly promoted the bone regeneration of PDLSC sheets in ectopic models.Conclusion: AuNPs enhance the osteogenesis of PDLSC sheets by activating autophagy, and 45-nm AuNPs were more effective than 13-nm AuNPs. This study may provide an AuNP-based pretreatment strategy for improving the application of CST in bone repair and regeneration.Keywords: gold nanoparticles, cell sheet technology, bone regeneration, autophagyZhang YWang PWang YLi JQiao DChen RYang WYan FDove Medical Pressarticlegold nanoparticlescell sheet technologybone regenerationautophagyMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 16, Pp 61-73 (2021)
institution DOAJ
collection DOAJ
language EN
topic gold nanoparticles
cell sheet technology
bone regeneration
autophagy
Medicine (General)
R5-920
spellingShingle gold nanoparticles
cell sheet technology
bone regeneration
autophagy
Medicine (General)
R5-920
Zhang Y
Wang P
Wang Y
Li J
Qiao D
Chen R
Yang W
Yan F
Gold Nanoparticles Promote the Bone Regeneration of Periodontal Ligament Stem Cell Sheets Through Activation of Autophagy
description Yangheng Zhang,1,* Peng Wang,2,* Yuxian Wang,3,* Jiao Li,4 Dan Qiao,1 Rixin Chen,1 Wenrong Yang,5 Fuhua Yan1 1Department of Periodontology, Nanjing Stomatological Hospital, Medical School of Nanjing University, Nanjing, Jiangsu, People’s Republic of China; 2State Key Laboratory of Pharmaceutical Biotechnology, Department of Sports Medicine and Adult Reconstructive Surgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, Jiangsu, People’s Republic of China; 3College of Biotechnology and Pharmaceutical Engineering, Nanjing Tech University, Nanjing, Jiangsu, People’s Republic of China; 4Department of Orthodontics, Nanjing Stomatological Hospital, Medical School of Nanjing University, Nanjing, Jiangsu, People’s Republic of China; 5School of Life and Environmental Science, Centre for Chemistry and Biotechnology, Deakin University, Geelong, VIC, Australia*These authors contributed equally to this workCorrespondence: Fuhua YanNanjing Stomatological Hospital, Medical School of Nanjing University, 30 Zhongyang Road, Nanjing, Jiangsu 210008, People’s Republic of ChinaTel +86 25 8362 0253Fax +86 25 8362 0202Email yanfh@nju.edu.cnObjective: Cell sheet technology (CST) is advantageous for repairing alveolar bone defects in clinical situations, and osteogenic induction before implantation may result in enhanced bone regeneration. Herein, we observed the effect of gold nanoparticles (AuNPs) on osteogenic differentiation of periodontal ligament stem cell (PDLSC) sheets and explored their potential mechanism of action.Methods: PDLSCs were cultured in cell sheet induction medium to obtain cell sheets. PDLSC sheets were treated with or without AuNPs. Alkaline phosphatase, alizarin red S, von Kossa, and immunofluorescence staining were used to observe the effects of AuNPs on the osteogenic differentiation of PDLSC sheets. Western blotting was performed to evaluate the osteogenic effects and autophagy activity. The cell sheets were transplanted into the dorsa of nude mice, and bone regeneration was analyzed by micro-CT and histological staining.Results: AuNPs could promote the osteogenic differentiation of PDLSC sheets by upregulating bone-related protein expression and mineralization. The 45-nm AuNPs were more effective than 13-nm AuNPs. Additional analysis demonstrated that their ability to promote differentiation could depend on activation of the autophagy pathway through upregulation of microtubule-associated protein light chain 3 and downregulation of sequestosome 1/p62. Furthermore, AuNPs significantly promoted the bone regeneration of PDLSC sheets in ectopic models.Conclusion: AuNPs enhance the osteogenesis of PDLSC sheets by activating autophagy, and 45-nm AuNPs were more effective than 13-nm AuNPs. This study may provide an AuNP-based pretreatment strategy for improving the application of CST in bone repair and regeneration.Keywords: gold nanoparticles, cell sheet technology, bone regeneration, autophagy
format article
author Zhang Y
Wang P
Wang Y
Li J
Qiao D
Chen R
Yang W
Yan F
author_facet Zhang Y
Wang P
Wang Y
Li J
Qiao D
Chen R
Yang W
Yan F
author_sort Zhang Y
title Gold Nanoparticles Promote the Bone Regeneration of Periodontal Ligament Stem Cell Sheets Through Activation of Autophagy
title_short Gold Nanoparticles Promote the Bone Regeneration of Periodontal Ligament Stem Cell Sheets Through Activation of Autophagy
title_full Gold Nanoparticles Promote the Bone Regeneration of Periodontal Ligament Stem Cell Sheets Through Activation of Autophagy
title_fullStr Gold Nanoparticles Promote the Bone Regeneration of Periodontal Ligament Stem Cell Sheets Through Activation of Autophagy
title_full_unstemmed Gold Nanoparticles Promote the Bone Regeneration of Periodontal Ligament Stem Cell Sheets Through Activation of Autophagy
title_sort gold nanoparticles promote the bone regeneration of periodontal ligament stem cell sheets through activation of autophagy
publisher Dove Medical Press
publishDate 2021
url https://doaj.org/article/522d8be746c744d988527768e9a0a9bc
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