TY - JOUR
T1 - EphB/ephrin-B interactions mediate human MSC attachment, migration and osteochondral differentiation
AU - Arthur, Agnieszka
AU - Zannettino, Andrew
AU - Panagopoulos, Romana
AU - Koblar, Simon A.
AU - Sims, Natalie A.
AU - Stylianou, Con
AU - Matsuo, Koichi
AU - Gronthos, Stan
N1 - Funding Information:
This study was supported by a Robinson Institute Research Grant in Aid and NHMRC Project Grant # 565176 .
PY - 2011/3/1
Y1 - 2011/3/1
N2 - 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.
AB - 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.
KW - Bone
KW - Cartilage
KW - Eph
KW - Ephrin
KW - Mesenchymal stem cell
KW - Stem cell
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UR - http://www.scopus.com/inward/citedby.url?scp=79751533475&partnerID=8YFLogxK
U2 - 10.1016/j.bone.2010.10.180
DO - 10.1016/j.bone.2010.10.180
M3 - Article
C2 - 21056708
AN - SCOPUS:79751533475
SN - 8756-3282
VL - 48
SP - 533
EP - 542
JO - Bone
JF - Bone
IS - 3
ER -
