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...
Main Authors: | , , , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
Dove Medical Press
2021-02-01
|
Series: | International Journal of Nanomedicine |
Subjects: | |
Online Access: | https://www.dovepress.com/the-role-and-activation-mechanism-of-taz-in-hierarchical-microgroovena-peer-reviewed-article-IJN |
id |
doaj-260a35df4c2846899847bd0096e49205 |
---|---|
record_format |
Article |
spelling |
doaj-260a35df4c2846899847bd0096e492052021-04-02T18:37:26ZengDove Medical PressInternational Journal of Nanomedicine1178-20132021-02-01Volume 161021103661988The Role and Activation Mechanism of TAZ in Hierarchical Microgroove/Nanopore Topography-Mediated Regulation of Stem Cell DifferentiationHu PGao QZheng HTian YZheng GYao XZhang JWu XSui LPenghui 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 differentiationhttps://www.dovepress.com/the-role-and-activation-mechanism-of-taz-in-hierarchical-microgroovena-peer-reviewed-article-IJNtazhierarchical micro/nanoscale topographyperiodontal ligament stem cellsosteogenic differentiationadipogenic differentiation |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Hu P Gao Q Zheng H Tian Y Zheng G Yao X Zhang J Wu X Sui L |
spellingShingle |
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 International Journal of Nanomedicine taz hierarchical micro/nanoscale topography periodontal ligament stem cells osteogenic differentiation adipogenic differentiation |
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 |
series |
International Journal of Nanomedicine |
issn |
1178-2013 |
publishDate |
2021-02-01 |
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 |
topic |
taz hierarchical micro/nanoscale topography periodontal ligament stem cells osteogenic differentiation adipogenic differentiation |
url |
https://www.dovepress.com/the-role-and-activation-mechanism-of-taz-in-hierarchical-microgroovena-peer-reviewed-article-IJN |
work_keys_str_mv |
AT hup theroleandactivationmechanismoftazinhierarchicalmicrogroovenanoporetopographymediatedregulationofstemcelldifferentiation AT gaoq theroleandactivationmechanismoftazinhierarchicalmicrogroovenanoporetopographymediatedregulationofstemcelldifferentiation AT zhengh theroleandactivationmechanismoftazinhierarchicalmicrogroovenanoporetopographymediatedregulationofstemcelldifferentiation AT tiany theroleandactivationmechanismoftazinhierarchicalmicrogroovenanoporetopographymediatedregulationofstemcelldifferentiation AT zhengg theroleandactivationmechanismoftazinhierarchicalmicrogroovenanoporetopographymediatedregulationofstemcelldifferentiation AT yaox theroleandactivationmechanismoftazinhierarchicalmicrogroovenanoporetopographymediatedregulationofstemcelldifferentiation AT zhangj theroleandactivationmechanismoftazinhierarchicalmicrogroovenanoporetopographymediatedregulationofstemcelldifferentiation AT wux theroleandactivationmechanismoftazinhierarchicalmicrogroovenanoporetopographymediatedregulationofstemcelldifferentiation AT suil theroleandactivationmechanismoftazinhierarchicalmicrogroovenanoporetopographymediatedregulationofstemcelldifferentiation AT hup roleandactivationmechanismoftazinhierarchicalmicrogroovenanoporetopographymediatedregulationofstemcelldifferentiation AT gaoq roleandactivationmechanismoftazinhierarchicalmicrogroovenanoporetopographymediatedregulationofstemcelldifferentiation AT zhengh roleandactivationmechanismoftazinhierarchicalmicrogroovenanoporetopographymediatedregulationofstemcelldifferentiation AT tiany roleandactivationmechanismoftazinhierarchicalmicrogroovenanoporetopographymediatedregulationofstemcelldifferentiation AT zhengg roleandactivationmechanismoftazinhierarchicalmicrogroovenanoporetopographymediatedregulationofstemcelldifferentiation AT yaox roleandactivationmechanismoftazinhierarchicalmicrogroovenanoporetopographymediatedregulationofstemcelldifferentiation AT zhangj roleandactivationmechanismoftazinhierarchicalmicrogroovenanoporetopographymediatedregulationofstemcelldifferentiation AT wux roleandactivationmechanismoftazinhierarchicalmicrogroovenanoporetopographymediatedregulationofstemcelldifferentiation AT suil roleandactivationmechanismoftazinhierarchicalmicrogroovenanoporetopographymediatedregulationofstemcelldifferentiation |
_version_ |
1721551491978756096 |