Journal article
EphrinB2 signaling in osteoblasts promotes bone mineralization by preventing apoptosis
S Tonna, FM Takyar, C Vrahnas, B Crimeen-Irwin, PWM Ho, IJ Poulton, HJ Brennan, NE McGregor, EH Allan, H Nguyen, MR Forwood, L Tatarczuch, EJ Mackie, TJ Martin, NA Sims
FASEB Journal | Published : 2014
DOI: 10.1096/fj.14-254300
Abstract
Cells that form bone (osteoblasts) express both ephrinB2 and EphB4, and previous work has shown that pharmacological inhibition of the ephrinB2/ EphB4 interaction impairs osteoblast differentiation in vitro and in vivo. The purpose of this study was to determine the role of ephrinB2 signaling in the osteoblast lineage in the process of bone formation. Cultured osteoblasts from mice with osteoblast-specific ablation of ephrinB2 showed delayed expression of osteoblast differentiation markers, a finding that was reproduced by ephrinB2, but not EphB4, RNA interference. Microcomputed tomography, histomorphometry, and mechanical testing of the mice lacking ephrinB2 in osteoblasts revealed a 2-fold..
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Funding Acknowledgements
The authors thank Joshua Johnson for technical assistance, St. Vincent's BioResources Centre staff for animal care, and Carl Walkley and Brian Liddicoat for helpful advice and assistance with the preparation of lenti-Cre reagents. This work was supported by National Health and Medical Research Council (NHMRC; Australia) project grants 620600 and 1042129; N.A.S. is supported by an NHMRC Senior Research Fellowship. S.T. is supported by an NHMRC Peter Doherty Postdoctoral Fellowship. F.T. was supported by a University of Melbourne at Melbourne Research Scholarship, a Melbourne International Fee Remission Scholarship, and a St. Vincent's Institute Foundation Scholarship. St. Vincent's Institute receives support from the Victorian State Government Operational Infrastructure Program. N.A.S. and T.J.M. jointly conceived the study; S.T., F.M.T., C.V., B.C.-I., P.W.M.H., N.E.M., E.H.A., I.J.P., and H.J.B. performed experiments and carried out analyses; H.N. and M.J.F. carried out 3-point bending tests with C.V. and provided interpretation; L.T. and E.J.M. carried out TEM analysis and provided interpretation; N.A.S., T.J.M., and S.T. wrote the manuscript; all authors discussed the results and commented on the manuscript at all stages. The authors declare no conflicts of interest.