Disturbed Expression of EphB4, but Not EphrinB2, Inhibited Bone Regeneration in an In Vivo Inflammatory Microenvironment

The important role of ephrinB2-EphB4 signaling pathway in bone remodeling has been well established. However, it is still unclear whether this bidirectional signaling also has effects on the regenerative processes of bone defects created in an inflammatory microenvironment. In this study, an experim...

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Main Authors: Li-Li Shen, Li-Xia Zhang, Li-Mei Wang, Rong-Jing Zhou, Cheng-Zhe Yang, Jin Zhang, Pi-Shan Yang
Format: Article
Language:English
Published: Wiley 2016-01-01
Series:Mediators of Inflammation
Online Access:http://dx.doi.org/10.1155/2016/6430407
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author Li-Li Shen
Li-Xia Zhang
Li-Mei Wang
Rong-Jing Zhou
Cheng-Zhe Yang
Jin Zhang
Pi-Shan Yang
author_facet Li-Li Shen
Li-Xia Zhang
Li-Mei Wang
Rong-Jing Zhou
Cheng-Zhe Yang
Jin Zhang
Pi-Shan Yang
author_sort Li-Li Shen
collection DOAJ
description The important role of ephrinB2-EphB4 signaling pathway in bone remodeling has been well established. However, it is still unclear whether this bidirectional signaling also has effects on the regenerative processes of bone defects created in an inflammatory microenvironment. In this study, an experimental animal model of bone defects treated with lentiviruses was prepared and an inflammatory microenvironment was established. Expression levels of bone marker genes were monitored in the newly formed bone tissue using quantitative reverse transcriptase polymerase chain reaction and western blot. Immunohistochemical (IHC) staining and histomorphometric analysis were also performed to evaluate bone healing processes. Compared with the pLenti6.3-ctrl group, the pLenti6.3-ephb4siRNA group exhibited lower expression levels of bone formation marker genes and a higher level of NFATc1 in the new bone tissue. In addition, the newly formed bone was thinner and the number of giant osteoclasts was higher in the pLenti6.3-ephb4siRNA group than that in the pLenti6.3-ctrl group. In contrast, there was no significant difference between the pLenti6.3-efnb2siRNA group and the pLenti6.3-ctrl group. In conclusion, EphB4 plays an irreplaceable role in bone regeneration in an inflammatory microenvironment, whereas the functional loss of ephrinB2 can be effectively compensated, most possibly by other ephrins with similar chemical structures.
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spelling doaj-art-167ceaff2a2f4e49a1fbc91486e85e872025-08-20T02:02:33ZengWileyMediators of Inflammation0962-93511466-18612016-01-01201610.1155/2016/64304076430407Disturbed Expression of EphB4, but Not EphrinB2, Inhibited Bone Regeneration in an In Vivo Inflammatory MicroenvironmentLi-Li Shen0Li-Xia Zhang1Li-Mei Wang2Rong-Jing Zhou3Cheng-Zhe Yang4Jin Zhang5Pi-Shan Yang6Shandong Provincial Key Laboratory of Oral Tissue Regeneration, Shandong University, Jinan, Shandong, ChinaShandong Provincial Key Laboratory of Oral Tissue Regeneration, Shandong University, Jinan, Shandong, ChinaShandong Provincial Key Laboratory of Oral Tissue Regeneration, Shandong University, Jinan, Shandong, ChinaLiaocheng People’s Hospital, Liaocheng, Shandong, ChinaDepartment of Oral & Maxillofacial Surgery, Qilu Hospital and Institute of Stomatology, Shandong University, Jinan, Shandong, ChinaShandong Provincial Key Laboratory of Oral Tissue Regeneration, Shandong University, Jinan, Shandong, ChinaShandong Provincial Key Laboratory of Oral Tissue Regeneration, Shandong University, Jinan, Shandong, ChinaThe important role of ephrinB2-EphB4 signaling pathway in bone remodeling has been well established. However, it is still unclear whether this bidirectional signaling also has effects on the regenerative processes of bone defects created in an inflammatory microenvironment. In this study, an experimental animal model of bone defects treated with lentiviruses was prepared and an inflammatory microenvironment was established. Expression levels of bone marker genes were monitored in the newly formed bone tissue using quantitative reverse transcriptase polymerase chain reaction and western blot. Immunohistochemical (IHC) staining and histomorphometric analysis were also performed to evaluate bone healing processes. Compared with the pLenti6.3-ctrl group, the pLenti6.3-ephb4siRNA group exhibited lower expression levels of bone formation marker genes and a higher level of NFATc1 in the new bone tissue. In addition, the newly formed bone was thinner and the number of giant osteoclasts was higher in the pLenti6.3-ephb4siRNA group than that in the pLenti6.3-ctrl group. In contrast, there was no significant difference between the pLenti6.3-efnb2siRNA group and the pLenti6.3-ctrl group. In conclusion, EphB4 plays an irreplaceable role in bone regeneration in an inflammatory microenvironment, whereas the functional loss of ephrinB2 can be effectively compensated, most possibly by other ephrins with similar chemical structures.http://dx.doi.org/10.1155/2016/6430407
spellingShingle Li-Li Shen
Li-Xia Zhang
Li-Mei Wang
Rong-Jing Zhou
Cheng-Zhe Yang
Jin Zhang
Pi-Shan Yang
Disturbed Expression of EphB4, but Not EphrinB2, Inhibited Bone Regeneration in an In Vivo Inflammatory Microenvironment
Mediators of Inflammation
title Disturbed Expression of EphB4, but Not EphrinB2, Inhibited Bone Regeneration in an In Vivo Inflammatory Microenvironment
title_full Disturbed Expression of EphB4, but Not EphrinB2, Inhibited Bone Regeneration in an In Vivo Inflammatory Microenvironment
title_fullStr Disturbed Expression of EphB4, but Not EphrinB2, Inhibited Bone Regeneration in an In Vivo Inflammatory Microenvironment
title_full_unstemmed Disturbed Expression of EphB4, but Not EphrinB2, Inhibited Bone Regeneration in an In Vivo Inflammatory Microenvironment
title_short Disturbed Expression of EphB4, but Not EphrinB2, Inhibited Bone Regeneration in an In Vivo Inflammatory Microenvironment
title_sort disturbed expression of ephb4 but not ephrinb2 inhibited bone regeneration in an in vivo inflammatory microenvironment
url http://dx.doi.org/10.1155/2016/6430407
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