title: Disturbed Expression of EphB4, but Not EphrinB2, Inhibited Bone Regeneration in an In Vivo Inflammatory Microenvironment.
abstract: 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.
authors.affiliation: Shandong Provincial Key Laboratory of Oral Tissue Regeneration, Shandong University, Jinan, Shandong, China; Liaocheng People's Hospital, Liaocheng, Shandong, China.
authors.forename: Li-Li
authors.initials: LL
authors.lastname: Shen
authors.affiliation: Shandong Provincial Key Laboratory of Oral Tissue Regeneration, Shandong University, Jinan, Shandong, China; Jinan Stomatological Hospital, Jinan, Shandong, China.
authors.forename: Li-Xia
authors.initials: LX
authors.lastname: Zhang
authors.affiliation: Shandong Provincial Key Laboratory of Oral Tissue Regeneration, Shandong University, Jinan, Shandong, China; Department of Periodontology, School of Dentistry, Shandong University, Jinan, Shandong, China.
authors.forename: Li-Mei
authors.initials: LM
authors.lastname: Wang
authors.affiliation: Liaocheng People's Hospital, Liaocheng, Shandong, China.
authors.forename: Rong-Jing
authors.initials: RJ
authors.lastname: Zhou
authors.affiliation: Department of Oral & Maxillofacial Surgery, Qilu Hospital and Institute of Stomatology, Shandong University, Jinan, Shandong, China.
authors.forename: Cheng-Zhe
authors.initials: CZ
authors.lastname: Yang
authors.affiliation: Shandong Provincial Key Laboratory of Oral Tissue Regeneration, Shandong University, Jinan, Shandong, China; Department of Endodontology, School of Dentistry, Shandong University, Jinan, Shandong, China.
authors.forename: Jin
authors.identifier: 0000-0003-1544-9241
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Shandong Provincial Key Laboratory of Oral Tissue Regeneration, Shandong University, Jinan, Shandong, China; Department of Periodontology, School of Dentistry, Shandong University, Jinan, Shandong, China.
authors.forename: Pi-Shan
authors.identifier: 0000-0002-7326-9452
authors.initials: PS
authors.lastname: Yang
mesh_terms: D000818:Animals; D001861:Bone Regeneration; D016723:Bone Remodeling; D001842:Bone and Bones / Q000378:metabolism; D002454:Cell Differentiation; D004195:Disease Models, Animal; D005786:Gene Expression Regulation; D057809:HEK293 Cells; D006801:Humans; D007150:Immunohistochemistry; D007249:Inflammation; D016086:Lentivirus / Q000235:genetics; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D050778:NFATC Transcription Factors / Q000378:metabolism*; D010006:Osteoblasts / Q000378:metabolism; D010010:Osteoclasts / Q000378:metabolism; D010012:Osteogenesis; D034741:RNA, Small Interfering / Q000378:metabolism; D036183:Receptor, EphB2 / Q000378:metabolism*; D036224:Receptor, EphB4 / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D050778:NFATC Transcription Factors; C494005:Nfatc1 protein, mouse; D034741:RNA, Small Interfering; C586311:Ephb2 protein, mouse; C086681:Ephb4 protein, mouse; D036183:Receptor, EphB2; D036224:Receptor, EphB4