TAZ promotes the proliferation and osteogenic differentiation of human periodontal ligament stem cells via the p-SMAD3.

Abstract

OBJECTIVE:

This study aims to offer insights about the biological influence of TAZ, which is a transcriptional coactivator containing a PDZ-binding motif, upon the apoptosis, proliferation, and osteogenic differentiation of human periodontal ligament stem cells (h-PDLSCs).

METHODS:

We used the green fluorescence protein lentivirus infection system to knockdown or overexpress TAZ in h-PDLSCs. 5-ethynyl-2'-deoxyuridine (EdU) staining detected the proliferative activity, and h-PDLSC apoptosis was analyzed by Annexin V-APC staining. TAZ knockdown or overexpression was performed to determine the osteogenic differentiation function of TAZ during the osteogenic induction of h-PDLSCs. The molecular mechanism of TAZ in the promotion of h-PDLSC osteogenesis was also explored. The chemical inhibitor of SMAD2/3 SIS3 HCL was used to identify the effects in vitro osteogenic differentiation and bone formation in h-PDLSCs overexpressing TAZ.

RESULTS:

TAZ overexpression resulted in enhanced cell rapid multiplication, which increased the expression of messenger RNA in stemness-related genes. By comparison, TAZ knockdown reduced proliferative activity and increased the apoptosis of h-PDLSCs. After the 7-day osteogenic induction period, alkaline phosphatase activity in the TAZ-overexpression group was significantly increased, and mineralized nodules increased significantly after osteogenic induction for 21 days. Similarly, osteoblast differentiation of h-PDLSCs was impaired after TAZ knockdown. However, the osteogenic potential of the group exposed to the p-SMAD3 inhibitor was restored to its original level.

CONCLUSION:

Hippo/TAZ plays a positive role inside the proliferation, stemness maintenance, and osteogenic specialization of h-PDLSCs, and the specific downstream factor of osteogenic differentiation is SMAD3.

• Authors: Ke Gu, Xucheng Fu, Hui Tian, Yafei Zhang, Aonan Li, Ying Wang, Yong Wen, Weiting Gu
• Journal: Journal of cellular biochemistry (J Cell Biochem) Vol. 121 Issue 2 Pg. 1101-1113 (02 2020) ISSN: 1097-4644 [Electronic] United States
• PMID: 31478222 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2019 Wiley Periodicals, Inc.

Chemical References

• Trans-Activators
• Transcriptional Coactivator with PDZ-Binding Motif Proteins
• WWTR1 protein, human

Topics

• Cell Differentiation
• Cell Proliferation
• Humans
• Osteogenesis
• Periodontal Ligament (cytology, metabolism)
• Stem Cells (cytology, metabolism)
• Trans-Activators (biosynthesis, genetics)
• Transcriptional Coactivator with PDZ-Binding Motif Proteins