EphB/ephrin-B interactions mediate human MSC attachment, migration and osteochondral differentiation

Agnieszka Arthur, Andrew Zannettino, Romana Panagopoulos, Simon A. Koblar, Natalie A. Sims, Con Stylianou, Koichi Matsuo, Stan Gronthos

Research output: Contribution to journalArticle

63 Citations (Scopus)

Abstract

Bone marrow derived mesenchymal stem/stromal cells (MSC) contribute to skeletal tissue formation and the regulation of haematopoiesis. The Eph/ephrin family of receptor tyrosine kinases is potentially important in the maintenance of the stem cell niche within neural, intestinal and dental tissues and has recently been shown to play a role in regulating bone homeostasis. However, the contribution of EphB/ephrin-B molecules in human MSC function remains to be determined. In the present study, EphB and ephrin-B molecules were expressed by ex vivo expanded human MSC populations and within human bone marrow trephine samples. To elucidate the contribution of EphB/ephrin-B molecules in MSC recruitment, we performed functional spreading and migration assays and showed that reverse ephrin-B signalling inhibited MSC attachment and spreading by activating Src-, PI3Kinase- and JNK-dependent signalling pathways. In contrast, forward EphB2 signalling promoted MSC migration by activating the Src kinase- and Abl-dependent signalling pathways. Furthermore, activation of ephrin-B1 and/or ephrin-B2 molecules expressed by MSC was found to increase osteogenic differentiation, while ephrin-B1 activation promoted chondrogenic differentiation. These observations suggest that EphB/ephrin-B interactions may mediate the recruitment, migration and differentiation of MSC during bone repair.

Original languageEnglish
Pages (from-to)533-542
Number of pages10
JournalBone
Volume48
Issue number3
DOIs
Publication statusPublished - 2011 Mar 1

Keywords

  • Bone
  • Cartilage
  • Eph
  • Ephrin
  • Mesenchymal stem cell
  • Stem cell

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Physiology
  • Histology

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    Arthur, A., Zannettino, A., Panagopoulos, R., Koblar, S. A., Sims, N. A., Stylianou, C., Matsuo, K., & Gronthos, S. (2011). EphB/ephrin-B interactions mediate human MSC attachment, migration and osteochondral differentiation. Bone, 48(3), 533-542. https://doi.org/10.1016/j.bone.2010.10.180