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

60 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

Fingerprint

Ephrins
Mesenchymal Stromal Cells
Cell Movement
Ephrin-B1
Eph Family Receptors
Ephrin-B2
Bone Marrow
Stem Cell Niche
Bone and Bones
src-Family Kinases
MAP Kinase Signaling System

Keywords

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

ASJC Scopus subject areas

  • Physiology
  • Endocrinology, Diabetes and Metabolism
  • Histology

Cite this

Arthur, A., Zannettino, A., Panagopoulos, R., Koblar, S. A., Sims, N. A., Stylianou, C., ... 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

EphB/ephrin-B interactions mediate human MSC attachment, migration and osteochondral differentiation. / Arthur, Agnieszka; Zannettino, Andrew; Panagopoulos, Romana; Koblar, Simon A.; Sims, Natalie A.; Stylianou, Con; Matsuo, Koichi; Gronthos, Stan.

In: Bone, Vol. 48, No. 3, 01.03.2011, p. 533-542.

Research output: Contribution to journalArticle

Arthur, A, Zannettino, A, Panagopoulos, R, Koblar, SA, Sims, NA, Stylianou, C, Matsuo, K & Gronthos, S 2011, 'EphB/ephrin-B interactions mediate human MSC attachment, migration and osteochondral differentiation', Bone, vol. 48, no. 3, pp. 533-542. https://doi.org/10.1016/j.bone.2010.10.180
Arthur A, Zannettino A, Panagopoulos R, Koblar SA, Sims NA, Stylianou C et al. EphB/ephrin-B interactions mediate human MSC attachment, migration and osteochondral differentiation. Bone. 2011 Mar 1;48(3):533-542. https://doi.org/10.1016/j.bone.2010.10.180
Arthur, Agnieszka ; Zannettino, Andrew ; Panagopoulos, Romana ; Koblar, Simon A. ; Sims, Natalie A. ; Stylianou, Con ; Matsuo, Koichi ; Gronthos, Stan. / EphB/ephrin-B interactions mediate human MSC attachment, migration and osteochondral differentiation. In: Bone. 2011 ; Vol. 48, No. 3. pp. 533-542.
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