Transgenic expression of ephrinB2 in periodontal ligament stem cells (<scp>PDLSC</scp>s) modulates osteogenic differentiation via signaling crosstalk between ephrinB2 and EphB4 in <scp>PDLSC</scp>s and between <scp>PDLSC</scp>s and pre‐osteoblasts within co‐culture

Zhu, Shi-Yao; Wang, P. L.; Liao, Chongshan; Yang, Yanqi; Yuan, Changyong; Wang, S.; Dissanayaka, Waruna Lakmal; Heng, Boon Chin; Zhang, C. F.

doi:10.1111/jre.12424

Cited by 23 publications

(26 citation statements)

References 34 publications

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“…In addition, ephrinB2-Fc can bind to EphB4 receptors on the surface of endothelial cells and promote the migration of vascular endothelial cells by activating the phosphatidylinositol 3-kinase signaling pathway to accelerate angiogenesis (10)(11)(12). Our previous experiments verified that ephrinB2 gene-transfected dental stem cells enhanced the osteogenic ability and promoted the angiogenesis of peripheral vascular endothelial cells (13), as well as promoted their angiogenesis in co-culture systems (14).…”

Section: Bidirectional Ephrinb2-ephb4 Signaling Regulates the Osteogesupporting

confidence: 69%

“…Indeed, in animal experiments, it has been demonstrated that the degree of bone mineralization, bone hardness and osteoblast differentiation in ephrinB2-deficient mice was significantly reduced compared with those in wild-type mice (34). Our previous study revealed that that ALP activity of PDLSCs was significantly increased following transfection with ephrinB2 in vitro, which resulted in more calcified nodules and increased expression levels of osteogenesis-associated genes (BSP, cOL1, Runx2, dSPP and OcN), suggesting that upregulation of ephrinB2 promoted the osteogenic differentiation of PdLScs (13). collectively, these previous results suggested that ephrinB2 is a potentially useful biomolecule for tissue engineering.…”

Section: Discussionmentioning

confidence: 92%

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Bidirectional ephrinB2‑EphB4 signaling regulates the osteogenic differentiation of canine periodontal ligament stem cells

et al. 2020

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The aim of the present study was to evaluate the effect of ephrinB2 gene-transfected canine periodontal ligament stem cells (cPdLScs) on the regulation of osteogenic differentiation. cPdLScs were transfected with a transgenic null-control green fluorescent protein (GFP) vector (termed Vector-cPDLSCs) or with NFNB2 GFP-Blasticidin (termed EfnB2-cPdLScs). Subsequently, the osteogenic differentiation of Vector-cPdLScs and EfnB2-cPdLScs was assessed by reverse transcription-quantitative polymerase chain reaction (RT-qPcR), alkaline phosphatase (ALP) assay and Alizarin Red S staining. The migratory abilities of cPdLScs, Vector-cPdLScs and EfnB2-cPdLScs were also assessed. Following osteogenic induction of Vector-cPdLScs and EfnB2-cPdLScs, the protein expression levels of collagen I, Runt-related transcription factor 2, osteocalcin, ephrin type-B receptor 4 (EphB4), phospho-EphB4, ephrinB2 and phospho-ephrinB2 were analyzed by western blot assays. Following gene transfection, the RT-qPcR and western blotting results revealed that the mRNA and protein expression levels of ephrinB2, respectively, were significantly increased in EfnB2-cPdLScs compared with that in Vector-cPdLScs (P<0.05). ALP and Alizarin Red S staining assays revealed increased ALP activity and mineralization nodules, respectively, in EfnB2-cPdLScs. cell proliferation and migration assays revealed that EfnB2-cPdLScs exhibited enhanced proliferation and migration compared with Vector-cPdLScs (P<0.05). In conclusion, the findings of the current study indicated that ephrinB2 gene-modified cPDLSCs exhibited enhanced osteogenic differentiation, with the ephrinB2 reverse signaling and EphB4 forward signaling pathways serving a key role in this process. Furthermore, ephrinB2 gene modification was observed to promote the migration and proliferation of cPdLScs.

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Section: Bidirectional Ephrinb2-ephb4 Signaling Regulates the Osteogesupporting

confidence: 69%

Section: Discussionmentioning

confidence: 92%

Bidirectional ephrinB2‑EphB4 signaling regulates the osteogenic differentiation of canine periodontal ligament stem cells

et al. 2020

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“…15 The consistent results were also produced in our previous study where 0.01 and 0.1 ng/mL TNFα stimulated, while 10 ng/mL inhibited, osteogenic differentiation of murine ST2 cells. 14 EphB4 signaling has been proven to play an important role in osteogenesis, 24,26,27,32 nevertheless, whether it is involved in TNFα impaired osteogenic differentiation of pre-osteoblasts has not been studied. In the present study, we found that both mRNA and protein levels of EphB4 were significantly downregulated after TNFα treatment, which indicated that TNFα inhibits EphB4 signaling via downregulating the expression of EphB4.…”

Section: Discussionmentioning

confidence: 99%

“…25 In addition, transgenic expression of ephrinB2 in periodontal ligament stem cells could promote osteogenic differentiation via stimulation of the phosphorylation of ephrinB2 and EphB4. 26 More interestingly, our recent study showed that low concentration of TNFα-induced osteogenic differentiation of pre-osteoblasts via activated EphB4 signaling. 27 However, whether EphB4 signaling is involved in high concentration of TNFα impaired osteogenic differentiation of pre-osteoblasts has not been studied to our limited knowledge.…”

Section: Introductionmentioning

confidence: 94%

Tumor necrosis factor‐alpha inhibits osteogenic differentiation of pre‐osteoblasts by downregulation of EphB4 signaling via activated nuclear factor‐kappaB signaling pathway

Wang

Zhao

Zhang

et al. 2017

J of Periodontal Research

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Background and Objective The majority of experiments show that tumor necrosis factor‐alpha (TNF‐α) inhibits osteogenic differentiation of mesenchymal stem cells and pre‐osteoblasts by activated nuclear factor‐kappaB (NF‐κB) signaling. However, the underlying mechanisms by which NF‐κB signaling inhibits osteogenic differentiation are not fully understood. The aim of the present study was to investigate whether EphB4 signaling inhibition mediates the effects of TNF‐α‐activated NF‐κB signaling on osteogenic differentiation of pre‐osteoblasts. Material and Methods Murine MC3T3‐E1 pre‐osteoblasts were treated with 10 ng/mL of TNF‐α. NF‐κB inhibitor, pyrrolidine dithiocarbamate, was used to achieve NF‐κB signaling inhibition. EphB4 signaling was activated using ephrinB2‐fc. The mRNA expressions of runt related transcription factor 2 (Runx2), bone sialoprotein (BSP) and EphB4 were determined using reverse transcription‐polymerase chain reaction. The protein levels of Runx2, BSP, Col Ia1, osteopontin, EphB4, p‐NF‐κB p65 and NF‐κB p65 were evaluated using western blot assays. Alkaline phosphatase (ALP) activity in MC3T3‐E1 cells was evaluated by ALP activity kit, and mineral nodule formation was evaluated by Alizarin Red S staining. Results TNF‐α inhibited EphB4 expression, while it suppressed Runx2, BSP expression from gene and protein levels as well as ALP activity and mineral nodule formation in MC3T3‐E1 cells. Activation of EphB4 signaling by ephrinB2‐fc promoted osteogenic differentiation of MC3T3‐E1 cells, whereas TNF‐α impaired the osteogenic differentiation enhanced by ephrinB2‐fc. Pyrrolidine dithiocarbamate blocked the activation of NF‐κB signaling induced by TNF‐α, while it prevented the downregulation of Runx2, BSP and EphB4, induced by TNF‐α. Conclusion TNF‐α inhibits osteogenic differentiation of pre‐osteoblasts by downregulation of EphB4 signaling via activated NF‐κB signaling pathway.

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“…The hPDLSCs used in this study were a kind gift from Dr. Chongshan Liao (The University of Hong Kong), and have been previously characterized by our research group. 10 All experimental protocols involving the use of hPDLSCs were approved by the Institutional Review Board of The University of Hong Kong (UW13-120). hPDLSCs at passage 3-7 were used for all experiments.…”

Section: Cell Culturementioning

confidence: 99%

In vitro cytocompatibility and osteogenic potential of calcium silicate-based dental cements in a root canal-filling model

et al. 2019

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Objective To investigate the in vitro cytocompatibility and osteogenic potential of an experimental calcium silicate-based cement and the inflammatory response in human periodontal ligament stem cells (hPDLSCs). Methods Cellular responses, osteogenic-related gene expression, and the production of inflammatory cytokines including interleukin (IL)-6 and IL-8 were studied in hPDLSCs exposed to the experimental root canal-filling material C-Root, the commercial tricalcium silicate-based material BioRoot RCS, and the epoxy resin-based material AH Plus. Differences were analyzed using one-way ANOVA with Bonferroni-adjusted pairwise comparison. Results Exposure to BioRoot and C-Root caused time-dependent increases in cell proliferation. Significantly more mineralized nodules were formed in cells exposed to AH Plus and BioRoot compared with the negative control. Alkaline phosphatase (ALP) activity was significantly lower in AH Plus cells compared with negative control, BioRoot, and C-Root cells. ALP, osteocalcin (OCN), and runt-related transcription factor2 (RUNX2) mRNA expression levels were all significantly higher in C-Root compared with AH Plus cells at day 7. IL-6 and IL-8 levels differed significantly among the experimental groups, with the highest IL-8 levels in BioRoot cells at days 7 and 14. Conclusion The experimental root canal-filling material C-Root has similar in vitro cytocompatibility to BioRoot and better osteogenic potential than AH Plus.

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Transgenic expression of ephrinB2 in periodontal ligament stem cells (PDLSCs) modulates osteogenic differentiation via signaling crosstalk between ephrinB2 and EphB4 in PDLSCs and between PDLSCs and pre‐osteoblasts within co‐culture

Abstract: Our data indicate that transgenic expression of ephrinB2 in PDLSCs could promote osteogenic differentiation via stimulation of the phosphorylation of ephrinB2 and EphB4, which regulates cell communication between PDLSCs and between PDLSCs and pre-osteoblasts within co-culture.

Cited by 23 publications

References 34 publications

Bidirectional ephrinB2‑EphB4 signaling regulates the osteogenic differentiation of canine periodontal ligament stem cells

Bidirectional ephrinB2‑EphB4 signaling regulates the osteogenic differentiation of canine periodontal ligament stem cells

Tumor necrosis factor‐alpha inhibits osteogenic differentiation of pre‐osteoblasts by downregulation of EphB4 signaling via activated nuclear factor‐kappaB signaling pathway

In vitro cytocompatibility and osteogenic potential of calcium silicate-based dental cements in a root canal-filling model

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