EphB/ephrin-B interactions mediate human MSC attachment, migration and osteochondral differentiation.
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.
Mesenchymal Stem Cell Group, Department of Haematology, Institute of Medical and Veterinary Science/Hanson Institute and Centre for Stem Cell Research/Robinson Institute, University of Adelaide, Adelaide, SA, Australia. agnes.arthur@health.sa.gov.au
Agnieszka
A
Arthur
Andrew
A
Zannettino
Romana
R
Panagopoulos
Simon A
SA
Koblar
Natalie A
NA
Sims
Con
C
Stylianou
Koichi
K
Matsuo
Stan
S
Gronthos
D002448:Cell Adhesion; D002454:Cell Differentiation / Q000235:genetics; D002460:Cell Line; D002465:Cell Movement / Q000235:genetics; D020219:Chondrogenesis / Q000235:genetics; D036342:Ephrins / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation; D006801:Humans; D008024:Ligands; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000378:metabolism*; D010012:Osteogenesis / Q000235:genetics; D011485:Protein Binding; D036081:Receptors, Eph Family / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction
D036342:Ephrins; D008024:Ligands; D036081:Receptors, Eph Family