Lipopolysaccharide from Escherichia coli stimulates osteogenic differentiation of human periodontal ligament stem cells through Wnt/β‐catenin–induced TAZ elevation

Abstract

Human periodontal ligament stem cells (PDLSCs), a type of dental tissue–derived mesenchymal stem cells (MSCs), can be clinically applied in periodontal tissue regeneration to treat periodontitis, which is initiated and sustained by bacteria. Lipopolysaccharide (LPS), the major component of the outer membrane of gram‐negative bacteria, is a pertinent deleterious factor in the oral microenvironment. The aim of this study was to investigate the effect of LPS on the proliferation and osteogenic differentiation of PDLSCs, as well as the mechanisms involved. Proliferation and osteogenic differentiation of PDLSCs were detected under the stimulation of Escherichia coli–derived LPS. The data showed that E. coli–derived LPS did not affect the proliferation, viability, and cell cycle of PDLSCs. Furthermore, it promoted osteogenic differentiation with the activation of TAZ. Lentivirus‐mediated depletion of TAZ (transcriptional activator with a PDZ motif) was used to determine the role of TAZ on LPS‐induced enhancement of osteogenesis. PDLSCs cultured in osteogenic media with or without LPS and DKK1 (Wnt/β‐catenin pathway inhibitor) were used to determine the regulatory effect of Wnt signaling. We found that TAZ depletion offset LPS‐induced enhancement of osteogenesis. Moreover, treatment with DKK1 offset LPS‐induced TAZ elevation and osteogenic promotion. In conclusion, E. coli–derived LPS promoted osteogenic differentiation of PDLSCs by fortifying TAZ activity. The elevation and activation of TAZ were mostly mediated by the Wnt/β‐catenin pathway. PDLSC‐governed alveolar bone tissue regeneration was not necessarily reduced under bacterial conditions and could be modulated by Wnt and TAZ.

RETRACTED ARTICLE: Polydatin improves osteogenic differentiation of human bone mesenchymal stem cells by stimulating TAZ expression via BMP2-Wnt/β-catenin signaling pathway

“…When Wnt ligands bind the receptors LRP5/6 and Frizzled receptors, the classical Wnt/β-catenin pathway is activated, after which formation of the Wnt-fz-lrp6 complex (including Axin, APC, GSK3, and CK1) promotes the release of β-catenin [9][10][11][12][13]. Ultimately, β-catenin migrates to the nucleus, where it forms a complex with TCF/LEF to stimulate the expression of osteogenic genes, such as RUNX2, ALP, DLX5, and OCN [14,15]. Wnt3a, a ligand of Wnt, has been proven to bind BMP proteins to activate a series of downstream reactions and promote osteogenic differentiation of BMSCs [16].…”

Transcriptome profiling of avian pathogenicEscherichia coliand the mouse microvascular endothelial cell line bEnd.3 during interaction

“…In addition, Cdh5 controls Cldn5 by triggering its transcriptional repression via FoxO1 and β-catenin (Taddei et al, 2008). Transcriptome data in the present study revealed a significant decrease in FoxO1 expression during infection but only a slight increase in β-catenin expression, which may be related to the up-regulation of β-catenin protein levels and the activation of Wnt/β-catenin signaling by LPS (Xing et al, 2019). Moreover, Wnt/ β-catenin signaling was shown to be involved in BBB development, where its blockade decreased Cdh5 expression in primary ECs of newborn mouse brain but not in that of the adult (Hubner et al, 2018).…”

Role of YAP/TAZ in Cell Lineage Fate Determination and Related Signaling Pathways

“…As discussed in the previous section, mechanosensing of substrate stiffness via YAP/TAZ regulates differentiation of MSCs into either the adipogenic or osteogenic lineage. But, contrary to what occurs in the case of osteogenesis, adipogenic differentiation is promoted on soft substrates that are nonconducive to cell adhesion and formation of FAs and stress fibers (Ji et al, 2019;Xing et al, 2019). On stiff substrates, the cytoskeletal focal adhesion protein vinculin promotes nuclear localization of TAZ, which inhibits adipogenic differentiation (Kuroda et al, 2017).…”

“…Similarly, various pharmacologically active chemicals promote osteogenesis through activation of TAZ. These include TM-25659 (Jang et al, 2012), sodium butyrate (Fan et al, 2018), lipopolysaccharide (Xing et al, 2019), 1α,25-dihydroxyvitamin D3 (Ji et al, 2019), icariin (Wei et al, 2017;Ye et al, 2017), epicatechin gallate (ECG) (Byun et al, 2014b), phorbaketal A (Byun et al, 2012a), kaempferol (Byun et al, 2012b), and poncirin (Yoon et al, 2011).…”