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

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.

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