Please use this identifier to cite or link to this item: http://hdl.handle.net/2440/117648
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Type: Journal article
Title: The osteoprogenitor-specific loss of ephrinB1 results in an osteoporotic phenotype affecting the balance between bone formation and resorption
Author: Arthur, A.
Nguyen, T.
Paton, S.
Klisuric, A.
Zannettino, A.
Gronthos, S.
Citation: Scientific Reports, 2018; 8(1):12756-1-12756-12
Publisher: Nature Publishing Group
Issue Date: 2018
ISSN: 2045-2322
2045-2322
Statement of
Responsibility: 
Agnieszka Arthur, Thao M. Nguyen, Sharon Paton, Ana Klisuric, Andrew C. W. Zannettino and Stan Gronthos
Abstract: The present study investigated the effects of conditional deletion of ephrinB1 in osteoprogenitor cells driven by the Osterix (Osx) promoter, on skeletal integrity in a murine model of ovariectomy-induced (OVX) osteoporosis. Histomorphometric and μCT analyses revealed that loss of ephrinB1 in sham Osx:cre-ephrinB1fl/fl mice caused a reduction in trabecular bone comparable to OVX Osx:Cre mice, which was associated with a significant reduction in bone formation rates and decrease in osteoblast numbers. Interestingly, these observations were not exacerbated in OVX Osx:cre-ephrinB1fl/fl mice. Furthermore, sham Osx:cre-ephrinB1fl/fl mice displayed significantly higher osteoclast numbers and circulating degraded collagen type 1 compared to OVX Osx:Cre mice. Confirmation studies found that cultured monocytes expressing EphB2 formed fewer TRAP+ multinucleated osteoclasts and exhibited lower resorption activity in the presence of soluble ephrinB1-Fc compared to IgG control. This inhibition of osteoclast formation and function induced by ephrinB1-Fc was reversed in the presence of an EphB2 chemical inhibitor. Collectively, these observations suggest that ephrinB1, expressed by osteoprogenitors, influences bone loss during the development of osteoporosis, by regulating both osteoblast and osteoclast formation and function, leading to a loss of skeletal integrity.
Keywords: Cells, Cultured; Osteoclasts; Osteoblasts; Animals; Mice, Transgenic; Mice, Knockout; Mice; Osteoporosis; Bone Resorption; Disease Models, Animal; Ephrin-B1; Ephrin-B2; Recombinant Proteins; Ovariectomy; Cell Count; Female; Male; Promoter Regions, Genetic; Sp7 Transcription Factor
Rights: © The Author(s) 2018. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
RMID: 0030096486
DOI: 10.1038/s41598-018-31190-2
Grant ID: http://purl.org/au-research/grants/nhmrc/1083704
http://purl.org/au-research/grants/nhmrc/1042677
Appears in Collections:Medicine publications

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