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

Authors Hu P, Gao Q, Zheng H, Tian Y, Zheng G, Yao X, Zhang J, Wu X, Sui L

Received 22 September 2020

Accepted for publication 25 December 2020

Published 11 February 2021 Volume 2021:16 Pages 1021—1036

DOI https://doi.org/10.2147/IJN.S283406

Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 3

Editor who approved publication: Prof. Dr. Thomas J. Webster


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 work

Correspondence: Lei Sui
Department of Prosthodontics, Tianjin Medical University School and Hospital of Stomatology, Tianjin, People’s Republic of China
Email suilei@tmu.edu.cn

Purpose: 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

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