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N-acetylcysteine regulates dental follicle stem cell osteogenesis and alveolar bone repair via ROS scavenging

BACKGROUND: Dental follicle stem cells (DFSCs) show mesenchymal stem cell properties with the potential for alveolar bone regeneration. Stem cell properties can be impaired by reactive oxygen species (ROS), prompting us to examine the importance of scavenging ROS for stem cell-based tissue regenerat...

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Autores principales: Meng, Zhaosong, Liu, Jiacheng, Feng, Zhipeng, Guo, Shuling, Wang, Mingzhe, Wang, Zheng, Li, Zhe, Li, Hongjie, Sui, Lei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9461171/
https://www.ncbi.nlm.nih.gov/pubmed/36076278
http://dx.doi.org/10.1186/s13287-022-03161-y
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author Meng, Zhaosong
Liu, Jiacheng
Feng, Zhipeng
Guo, Shuling
Wang, Mingzhe
Wang, Zheng
Li, Zhe
Li, Hongjie
Sui, Lei
author_facet Meng, Zhaosong
Liu, Jiacheng
Feng, Zhipeng
Guo, Shuling
Wang, Mingzhe
Wang, Zheng
Li, Zhe
Li, Hongjie
Sui, Lei
author_sort Meng, Zhaosong
collection PubMed
description BACKGROUND: Dental follicle stem cells (DFSCs) show mesenchymal stem cell properties with the potential for alveolar bone regeneration. Stem cell properties can be impaired by reactive oxygen species (ROS), prompting us to examine the importance of scavenging ROS for stem cell-based tissue regeneration. This study aimed to investigate the effect and mechanism of N-acetylcysteine (NAC), a promising antioxidant, on the properties of DFSCs and DFSC-based alveolar bone regeneration. METHODS: DFSCs were cultured in media supplemented with different concentrations of NAC (0–10 mM). Cytologic experiments, RNA-sequencing and antioxidant assays were performed in vitro in human DFSCs (hDFSCs). Rat maxillary first molar extraction models were constructed, histological and radiological examinations were performed at day 7 post-surgery to investigate alveolar bone regeneration in tooth extraction sockets after local transplantation of NAC, rat DFSCs (rDFSCs) or NAC-treated rDFSCs. RESULTS: 5 mM NAC-treated hDFSCs exhibited better proliferation, less senescent rate, higher stem cell-specific marker and immune-related factor expression with the strongest osteogenic differentiation; other concentrations were also beneficial for maintaining stem cell properties. RNA-sequencing identified 803 differentially expressed genes between hDFSCs with and without 5 mM NAC. “Developmental process (GO:0032502)” was prominent, bioinformatic analysis of 394 involved genes revealed functional and pathway enrichment of ossification and PI3K/AKT pathway, respectively. Furthermore, after NAC treatment, the reduction of ROS levels (ROS, superoxide, hydrogen peroxide), the induction of antioxidant levels (glutathione, catalase, superoxide dismutase), the upregulation of PI3K/AKT signaling (PI3K-p110, PI3K-p85, AKT, phosphorylated-PI3K-p85, phosphorylated-AKT) and the rebound of ROS level upon PI3K/AKT inhibition were showed. Local transplantation of NAC, rDFSCs or NAC-treated rDFSCs was safe and promoted oral socket bone formation after tooth extraction, with application of NAC-treated rDFSCs possessing the best effect. CONCLUSIONS: The proper concentration of NAC enhances DFSC properties, especially osteogenesis, via PI3K/AKT/ROS signaling, and offers clinical potential for stem cell-based alveolar bone regeneration. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13287-022-03161-y.
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spelling pubmed-94611712022-09-10 N-acetylcysteine regulates dental follicle stem cell osteogenesis and alveolar bone repair via ROS scavenging Meng, Zhaosong Liu, Jiacheng Feng, Zhipeng Guo, Shuling Wang, Mingzhe Wang, Zheng Li, Zhe Li, Hongjie Sui, Lei Stem Cell Res Ther Research BACKGROUND: Dental follicle stem cells (DFSCs) show mesenchymal stem cell properties with the potential for alveolar bone regeneration. Stem cell properties can be impaired by reactive oxygen species (ROS), prompting us to examine the importance of scavenging ROS for stem cell-based tissue regeneration. This study aimed to investigate the effect and mechanism of N-acetylcysteine (NAC), a promising antioxidant, on the properties of DFSCs and DFSC-based alveolar bone regeneration. METHODS: DFSCs were cultured in media supplemented with different concentrations of NAC (0–10 mM). Cytologic experiments, RNA-sequencing and antioxidant assays were performed in vitro in human DFSCs (hDFSCs). Rat maxillary first molar extraction models were constructed, histological and radiological examinations were performed at day 7 post-surgery to investigate alveolar bone regeneration in tooth extraction sockets after local transplantation of NAC, rat DFSCs (rDFSCs) or NAC-treated rDFSCs. RESULTS: 5 mM NAC-treated hDFSCs exhibited better proliferation, less senescent rate, higher stem cell-specific marker and immune-related factor expression with the strongest osteogenic differentiation; other concentrations were also beneficial for maintaining stem cell properties. RNA-sequencing identified 803 differentially expressed genes between hDFSCs with and without 5 mM NAC. “Developmental process (GO:0032502)” was prominent, bioinformatic analysis of 394 involved genes revealed functional and pathway enrichment of ossification and PI3K/AKT pathway, respectively. Furthermore, after NAC treatment, the reduction of ROS levels (ROS, superoxide, hydrogen peroxide), the induction of antioxidant levels (glutathione, catalase, superoxide dismutase), the upregulation of PI3K/AKT signaling (PI3K-p110, PI3K-p85, AKT, phosphorylated-PI3K-p85, phosphorylated-AKT) and the rebound of ROS level upon PI3K/AKT inhibition were showed. Local transplantation of NAC, rDFSCs or NAC-treated rDFSCs was safe and promoted oral socket bone formation after tooth extraction, with application of NAC-treated rDFSCs possessing the best effect. CONCLUSIONS: The proper concentration of NAC enhances DFSC properties, especially osteogenesis, via PI3K/AKT/ROS signaling, and offers clinical potential for stem cell-based alveolar bone regeneration. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13287-022-03161-y. BioMed Central 2022-09-08 /pmc/articles/PMC9461171/ /pubmed/36076278 http://dx.doi.org/10.1186/s13287-022-03161-y Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open AccessThis 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 licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence 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 licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Meng, Zhaosong
Liu, Jiacheng
Feng, Zhipeng
Guo, Shuling
Wang, Mingzhe
Wang, Zheng
Li, Zhe
Li, Hongjie
Sui, Lei
N-acetylcysteine regulates dental follicle stem cell osteogenesis and alveolar bone repair via ROS scavenging
title N-acetylcysteine regulates dental follicle stem cell osteogenesis and alveolar bone repair via ROS scavenging
title_full N-acetylcysteine regulates dental follicle stem cell osteogenesis and alveolar bone repair via ROS scavenging
title_fullStr N-acetylcysteine regulates dental follicle stem cell osteogenesis and alveolar bone repair via ROS scavenging
title_full_unstemmed N-acetylcysteine regulates dental follicle stem cell osteogenesis and alveolar bone repair via ROS scavenging
title_short N-acetylcysteine regulates dental follicle stem cell osteogenesis and alveolar bone repair via ROS scavenging
title_sort n-acetylcysteine regulates dental follicle stem cell osteogenesis and alveolar bone repair via ros scavenging
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9461171/
https://www.ncbi.nlm.nih.gov/pubmed/36076278
http://dx.doi.org/10.1186/s13287-022-03161-y
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