The Role and Activation Mechanism of TAZ in Hierarchical Microgroove/Nanopore Topography-Mediated Regulation of Stem Cell Differentiation

Penghui Hu,1,2,* Qian Gao,1,2,* Huimin Zheng,1,2 Yujuan Tian,1,2 Guoying Zheng,1 Xiaoyu Yao,1 Junjiang Zhang,1 Xudong Wu,2 Lei Sui1 1Department of Prosthodontics, Tianjin Medical University School and Hospital of Stomatology, Tianjin, People’s Republic of China; 2Department of Cell Biology...

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Autores principales: Hu P, Gao Q, Zheng H, Tian Y, Zheng G, Yao X, Zhang J, Wu X, Sui L
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spelling oai:doaj.org-article:260a35df4c2846899847bd0096e492052021-12-02T13:50:52ZThe Role and Activation Mechanism of TAZ in Hierarchical Microgroove/Nanopore Topography-Mediated Regulation of Stem Cell Differentiation1178-2013https://doaj.org/article/260a35df4c2846899847bd0096e492052021-02-01T00:00:00Zhttps://www.dovepress.com/the-role-and-activation-mechanism-of-taz-in-hierarchical-microgroovena-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Penghui Hu,1,2,* Qian Gao,1,2,* Huimin Zheng,1,2 Yujuan Tian,1,2 Guoying Zheng,1 Xiaoyu Yao,1 Junjiang Zhang,1 Xudong Wu,2 Lei Sui1 1Department of Prosthodontics, Tianjin Medical University School and Hospital of Stomatology, Tianjin, People’s Republic of China; 2Department of Cell Biology, 2011 Collaborative Innovation Center of Tianjin for Medical Epigenetics, Tianjin Key Laboratory of Medical Epigenetics, Tianjin Medical University, Tianjin, People’s Republic of China*These authors contributed equally to this workCorrespondence: Lei SuiDepartment of Prosthodontics, Tianjin Medical University School and Hospital of Stomatology, Tianjin, People’s Republic of ChinaEmail suilei@tmu.edu.cnPurpose: To investigate the role and activation mechanism of TAZ in periodontal ligament stem cells (PDLSCs) perceiving hierarchical microgroove/nanopore topography.Materials and Methods: Titanium surface with hierarchical microgroove/nanopore topography fabricated by selective laser melting combined with alkali heat treatment (SLM-AHT) was used as experimental group, smooth titanium surface (Ti) and sandblasted, large-grit, acid-etched (SLA) titanium surface were employed as control groups. Alkaline phosphatase (ALP) activity assays, qRT-PCR, Western blotting, and immunofluorescence were carried out to evaluate the effect of SLM-AHT surface on PDLSC differentiation. Moreover, TAZ activation was investigated from the perspective of nuclear localization to transcriptional activity. TAZ knockdown PDLSCs were seeded on three titanium surfaces to detect osteogenesis- and adipogenesis-related gene expression levels. Immunofluorescence and Western blotting were employed to investigate the effect of the SLM-AHT surface on actin cytoskeletal polymerization and MAPK signaling pathway. Cytochalasin D and MAPK signaling pathway inhibitors were used to determine whether actin cytoskeletal polymerization and the MAPK signaling pathway were indispensable for TAZ activation.Results: Our results showed that SLM-AHT surface had a greater potential to promote PDLSC osteogenic differentiation while inhibiting adipogenic differentiation than the other two groups. The nuclear localization and transcriptional activity of TAZ were strongly enhanced on the SLM-AHT surface. Moreover, after TAZ knockdown, the enhanced osteogenesis and decreased adipogenesis in SLM-AHT group could not be observed. In addition, SLM-AHT surface could promote actin cytoskeletal polymerization and upregulate p-ERK and p-p38 protein levels. After treatment with cytochalasin D and MAPK signaling pathway inhibitors, differences in the TAZ subcellular localization and transcriptional activity were no longer observed among the different titanium surfaces.Conclusion: Our results demonstrated that actin cytoskeletal polymerization and MAPK signaling pathway activation triggered by SLM-AHT surface were essential for TAZ activation, which played a dominant role in SLM-AHT surface-induced stem cell fate decision.Keywords: TAZ, hierarchical micro/nanoscale topography, periodontal ligament stem cells, osteogenic differentiation, adipogenic differentiationHu PGao QZheng HTian YZheng GYao XZhang JWu XSui LDove Medical Pressarticletazhierarchical micro/nanoscale topographyperiodontal ligament stem cellsosteogenic differentiationadipogenic differentiationMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 16, Pp 1021-1036 (2021)
institution DOAJ
collection DOAJ
language EN
topic taz
hierarchical micro/nanoscale topography
periodontal ligament stem cells
osteogenic differentiation
adipogenic differentiation
Medicine (General)
R5-920
spellingShingle taz
hierarchical micro/nanoscale topography
periodontal ligament stem cells
osteogenic differentiation
adipogenic differentiation
Medicine (General)
R5-920
Hu P
Gao Q
Zheng H
Tian Y
Zheng G
Yao X
Zhang J
Wu X
Sui L
The Role and Activation Mechanism of TAZ in Hierarchical Microgroove/Nanopore Topography-Mediated Regulation of Stem Cell Differentiation
description Penghui Hu,1,2,* Qian Gao,1,2,* Huimin Zheng,1,2 Yujuan Tian,1,2 Guoying Zheng,1 Xiaoyu Yao,1 Junjiang Zhang,1 Xudong Wu,2 Lei Sui1 1Department of Prosthodontics, Tianjin Medical University School and Hospital of Stomatology, Tianjin, People’s Republic of China; 2Department of Cell Biology, 2011 Collaborative Innovation Center of Tianjin for Medical Epigenetics, Tianjin Key Laboratory of Medical Epigenetics, Tianjin Medical University, Tianjin, People’s Republic of China*These authors contributed equally to this workCorrespondence: Lei SuiDepartment of Prosthodontics, Tianjin Medical University School and Hospital of Stomatology, Tianjin, People’s Republic of ChinaEmail suilei@tmu.edu.cnPurpose: To investigate the role and activation mechanism of TAZ in periodontal ligament stem cells (PDLSCs) perceiving hierarchical microgroove/nanopore topography.Materials and Methods: Titanium surface with hierarchical microgroove/nanopore topography fabricated by selective laser melting combined with alkali heat treatment (SLM-AHT) was used as experimental group, smooth titanium surface (Ti) and sandblasted, large-grit, acid-etched (SLA) titanium surface were employed as control groups. Alkaline phosphatase (ALP) activity assays, qRT-PCR, Western blotting, and immunofluorescence were carried out to evaluate the effect of SLM-AHT surface on PDLSC differentiation. Moreover, TAZ activation was investigated from the perspective of nuclear localization to transcriptional activity. TAZ knockdown PDLSCs were seeded on three titanium surfaces to detect osteogenesis- and adipogenesis-related gene expression levels. Immunofluorescence and Western blotting were employed to investigate the effect of the SLM-AHT surface on actin cytoskeletal polymerization and MAPK signaling pathway. Cytochalasin D and MAPK signaling pathway inhibitors were used to determine whether actin cytoskeletal polymerization and the MAPK signaling pathway were indispensable for TAZ activation.Results: Our results showed that SLM-AHT surface had a greater potential to promote PDLSC osteogenic differentiation while inhibiting adipogenic differentiation than the other two groups. The nuclear localization and transcriptional activity of TAZ were strongly enhanced on the SLM-AHT surface. Moreover, after TAZ knockdown, the enhanced osteogenesis and decreased adipogenesis in SLM-AHT group could not be observed. In addition, SLM-AHT surface could promote actin cytoskeletal polymerization and upregulate p-ERK and p-p38 protein levels. After treatment with cytochalasin D and MAPK signaling pathway inhibitors, differences in the TAZ subcellular localization and transcriptional activity were no longer observed among the different titanium surfaces.Conclusion: Our results demonstrated that actin cytoskeletal polymerization and MAPK signaling pathway activation triggered by SLM-AHT surface were essential for TAZ activation, which played a dominant role in SLM-AHT surface-induced stem cell fate decision.Keywords: TAZ, hierarchical micro/nanoscale topography, periodontal ligament stem cells, osteogenic differentiation, adipogenic differentiation
format article
author Hu P
Gao Q
Zheng H
Tian Y
Zheng G
Yao X
Zhang J
Wu X
Sui L
author_facet Hu P
Gao Q
Zheng H
Tian Y
Zheng G
Yao X
Zhang J
Wu X
Sui L
author_sort Hu P
title The Role and Activation Mechanism of TAZ in Hierarchical Microgroove/Nanopore Topography-Mediated Regulation of Stem Cell Differentiation
title_short The Role and Activation Mechanism of TAZ in Hierarchical Microgroove/Nanopore Topography-Mediated Regulation of Stem Cell Differentiation
title_full The Role and Activation Mechanism of TAZ in Hierarchical Microgroove/Nanopore Topography-Mediated Regulation of Stem Cell Differentiation
title_fullStr The Role and Activation Mechanism of TAZ in Hierarchical Microgroove/Nanopore Topography-Mediated Regulation of Stem Cell Differentiation
title_full_unstemmed The Role and Activation Mechanism of TAZ in Hierarchical Microgroove/Nanopore Topography-Mediated Regulation of Stem Cell Differentiation
title_sort role and activation mechanism of taz in hierarchical microgroove/nanopore topography-mediated regulation of stem cell differentiation
publisher Dove Medical Press
publishDate 2021
url https://doaj.org/article/260a35df4c2846899847bd0096e49205
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