The balance of bone homeostasis is disrupted with the loss of ephrinB1 in osteoprogenitors, resulting in an osteoporotic phenotype. — ASN Events
  1. Schedule
  2. Welcome Reception & ANZBMS Plenary Posters
  3. The balance of bone homeostasis is disrupted with the loss of ephrinB1 in osteoprogenitors, resulting in an osteoporotic phenotype.

The balance of bone homeostasis is disrupted with the loss of ephrinB1 in osteoprogenitors, resulting in an osteoporotic phenotype. (#104)

Agnieszka Arthur 1 2 , Thao Nguyen 1 2 , Sharon Paton 1 2 , Andrew Zannettino 2 3 , Stan Gronthos 1 2
  1. Mesenchymal Stem Cell Laboratory, Adelaide Medical School, Faculty of Health and Medical Sciences, University of Adelaide, Adelaide, SA, Australia
  2. Precision Medicine Theme, South Australian Health and Medical Research Institute, Adelaide, SA, Australia
  3. Myeloma Research Laboratory, Adelaide Medical School, Faculty of Health and Medical Sciences, University of Adelaide, Adelaide, SA, Australia

Members of the Eph receptor tyrosine kinase family and their ephrin ligands are involved in the process of skeletal development and bone homeostasis in humans and mouse models. Our studies demonstrated that ephrinB1 expressed by human mesenchymal stem cells (MSC) when stimulated by the EphB2 receptor, promoted osteogenic differentiation. While in a mouse model, loss of ephrinB1 in osteoprogenitors resulted in impairment of endochondral ossification, compromising bone formation and integrity during skeletal maturation. The present study examined the importance of ephrinB1 during the maintenance of bone homeostasis following the onset of osteoporosis. Bone samples were analysed from ovariectomised-induced osteoporotic and non-osteoporotic female C57BL/6 mice and assessed for ephrinB expression by RT-PCR. Female homozygote ephrinB1 (EfnB1) conditional knockouts under the control of the osterix promoter (Osx:cre-ephrinB1fl/fl) and Osx:Cre controls were used to assess skeletal tissue parameters following ovariectomy-induced osteoporosis or sham surgery. To identify the contribution of Eph-ephrinB1 signalling in osteoclast function, human osteoclastogenic in vitro studies were performed and assessed by RT-PCR and TRAP enumeration. In a mouse ovariectomy model, ephrinB1 gene expression was significantly down-regulated compared to ephrinB2, compared to normal controls. We observed that Osx:EfnB1-/- sham treated mice displayed an osteoporotic bone phenotype. The loss of EfnB1 by osteoprogenitors alone impaired trabecular bone architecture similar to the ovariectomised Osx:Cre controls, which was not further exacerbated in Osx:cre-ephrinB1fl/flovariectomised females. This osteoporotic phenotype was correlated with a significant reduction in osteoblast and elevated osteoclast numbers within the bone. RT-PCR analysis identified EphB2 as the highest expressing EphB member by human PBMNC during osteoclast differentiation. Functionally, ephrinB1 stimulation of EphB2 expressing monocytes resulted in significantly fewer multinucleated TRAP+ osteoclasts following differentiation. These observations suggest that ephrinB1 signalling may be important in maintaining bone integrity, where loss of ephrinB1 in the osteogenic lineage can lead to an imbalance of bone homeostasis.