Lipopolysaccharide inhibits osteogenic differentiation of periodontal ligament stem cells partially through toll-like re
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ORIGINAL ARTICLE
Lipopolysaccharide inhibits osteogenic differentiation of periodontal ligament stem cells partially through toll-like receptor 4-mediated ephrinB2 downregulation Wen Wang 1 & Changyong Yuan 1 & Tengyu Geng 1 & Yi Liu 1 & Shaoyue Zhu 2 & Chengfei Zhang 2 & Zongxiang Liu 1 & Penglai Wang 1 Received: 22 November 2019 / Accepted: 9 January 2020 # Springer-Verlag GmbH Germany, part of Springer Nature 2020
Abstract Objectives This study aimed to investigate the possible crosstalk between LPS/toll-like receptor 4 (TLR4) and ephrinB2 signaling in mediating osteogenic differentiation of PDLSCs. Materials and methods Human periodontal ligament stem cells (hPDLSCs) were harvested and treated with different concentrations of LPS under osteogenic induction. qPCR, alkaline phosphatase (ALP) staining, and Alizarin Red S staining were performed to assess osteogenic gene expression, ALP activity, and mineralized nodule formation. EphrinB2 mRNA and protein expressions after LPS treatment were also determined. To explore the role of ephrinB2 in LPS-impaired osteogenic differentiation of hPDLSCs, hPDLSCs were stimulated with ephrinB2-Fc or transfected with ephrinB2 lentivirus, and then, the osteogenic differentiation capacity was evaluated. Results LPS inhibited osteogenic differentiation of hPDLSCs and downregulated ephrinB2 expression in hPDLSCs during osteogenic differentiation. Blockage of TLR4 partially reversed LPS-induced decrease in ephrinB2 expression. EphrinB2-Fc promoted mineralized nodule formation and increased the expression of ALP, osteocalcin (OCN), and bone morphogenetic protein 2 (BMP2) in hPDLSCs. EphrinB2-overexpressing hPDLSCs treated with LPS expressed higher ALP and BMP2 mRNA and higher ALP activity and showed more mineralized nodule formation, when compared with wide-type hPDLSCs treated with LPS. Conclusions Our data suggested that LPS decreased the osteogenic differentiation capacity of hPDLSCs partially through downregulation of ephrinB2 expression via LPS/TLR4 signaling. Upregulation of ephrinB2 partially reversed the impaired osteogenic potential of hPDLSCs induced by LPS. Clinical relevance Our results provided a new insight of mechanism underling LPS-mediated osteogenic differentiation inhibition of PDLSCs and clarified a potential target for the management of periodontitis. Keywords Periodontal ligament stem cells . Osteogenic differentiation . Lipopolysaccharide . EphrinB2
Introduction
Wen Wang and Changyong Yuan contributed equally to this work. * Zongxiang Liu [email protected] * Penglai Wang [email protected] 1
Affiliated Stomatological Hospital of Xuzhou Medical University, No. 130 Huaihai West Road, Xuzhou 221000, Jiangsu, China
2
Faculty of Dentistry, The University of Hong Kong, Pokfulam, Hong Kong 999077, China
Periodontal pathogenic bacteria (mainly Gram-negative anaerobes) trigger an inflammatory reaction in the toothsupporting tissues, causing periodontal and bone damage and subsequent tooth loss [1, 2]. Lipopolysaccharide (LPS), the major virulent factor of Gram-negati
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