Journal article

EphrinB2/EphB4 inhibition in the osteoblast lineage modifies the anabolic response to parathyroid hormone

Farzin M Takyar, Stephen Tonna, Patricia WM Ho, Blessing Crimeen-Irwin, Emma K Baker, T John Martin, Natalie A Sims



Previous reports indicate that ephrinB2 expression by osteoblasts is stimulated by parathyroid hormone (PTH) and its related protein (PTHrP) and that ephrinB2/EphB4 signaling between osteoblasts and osteoclasts stimulates osteoblast differentiation while inhibiting osteoclast differentiation. To determine the role of the ephrinB2/EphB4 interaction in the skeleton, we used a specific inhibitor, soluble EphB4 (sEphB4), in vitro and in vivo. sEphB4 treatment of cultured osteoblasts specifically inhibited EphB4 and ephrinB2 phosphorylation and reduced mRNA levels of late markers of osteoblast/osteocyte differentiation (osteocalcin, dentin matrix protein-1 [DMP-1], sclerostin, matrix-extracellula..

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Awarded by NHMRC (Australia)

Funding Acknowledgements

The authors acknowledge the excellent technical assistance of Narelle McGregor, Ingrid Poulton, and Joshua Johnson, and thank the St. Vincent's Bioresources Centre staff for excellent animal care. We thank V Krasnoperov for helpful advice and supply of sEphB4, and JM Quinn for advice on the NF kappa B-luciferase assay. The work was supported by NHMRC (Australia) Project Grant 620600 and supported in part by the Victorian Government OIS program; NAS is supported by an NHMRC (Australia) Senior Research Fellowship. FT is supported by a University of Melbourne Melbourne Research Scholarship, a Melbourne International Fee Remission Scholarship, and a St. Vincent's Institute Foundation Scholarship. ST is supported by an NHMRC (Australia) Peter Doherty Fellowship. EKB is supported by a Cure Cancer Australia Fellowship. The Osteomeasure system was purchased with the generous support of the Jack Brockhoff Foundation and purchase of the microCT system was partially supported by the Potter Foundation.