TY - JOUR
T1 - EphB/Ephrin-B interaction mediates adult stem cell attachment, spreading, and migration
T2 - Implications for dental tissue repair
AU - Stokowski, Agnieszka
AU - Shi, Songtao
AU - Sun, Tao
AU - Bartold, Peter Mark
AU - Koblar, Simon Andrea
AU - Gronthos, Stan
N1 - Copyright:
Copyright 2008 Elsevier B.V., All rights reserved.
PY - 2007/1
Y1 - 2007/1
N2 - Human adult dental pulp stem cells (DPSCs) reside predominantly within the perivascular niche of dental pulp and are thought to originate from migrating neural crest cells during development. The Eph family of receptor tyrosine kinases and their ligands, the ephrin molecules, play an essential role in the migration of neural crest cells during development and stem cell niche maintenance. The present study examined the expression and function of the B-subclass Eph/ephrin molecules on DPSCs. Multiple receptors were primarily identified on DPSCs within the perivascular niche, whereas ephrin-B1 and ephrin-B3 were expressed by the surrounding pulp tissue. EphB/ephrin-B bidirectional signaling inhibited cell attachment and spreading, predominately via the mitogen-activated protein kinase (MAPK) pathway for forward signaling and phosphorylation of Src family tyrosine kinases via reverse ephrin-B signaling. DPSC migration was restricted through unidirectional ephrin-B1-activated EphB forward signaling, primarily signaling through the MAPK pathway. Furthermore, we observed that ephrin-B1 was downregulated in diseased adult teeth compared with paired uninjured controls. Collectively, these studies suggest that EphB/ephrin-B molecules play a role in restricting DPSC attachment and migration to maintain DPSCs within their stem cell niche under steady-state conditions. These results may have implications for dental pulp development and regeneration.
AB - Human adult dental pulp stem cells (DPSCs) reside predominantly within the perivascular niche of dental pulp and are thought to originate from migrating neural crest cells during development. The Eph family of receptor tyrosine kinases and their ligands, the ephrin molecules, play an essential role in the migration of neural crest cells during development and stem cell niche maintenance. The present study examined the expression and function of the B-subclass Eph/ephrin molecules on DPSCs. Multiple receptors were primarily identified on DPSCs within the perivascular niche, whereas ephrin-B1 and ephrin-B3 were expressed by the surrounding pulp tissue. EphB/ephrin-B bidirectional signaling inhibited cell attachment and spreading, predominately via the mitogen-activated protein kinase (MAPK) pathway for forward signaling and phosphorylation of Src family tyrosine kinases via reverse ephrin-B signaling. DPSC migration was restricted through unidirectional ephrin-B1-activated EphB forward signaling, primarily signaling through the MAPK pathway. Furthermore, we observed that ephrin-B1 was downregulated in diseased adult teeth compared with paired uninjured controls. Collectively, these studies suggest that EphB/ephrin-B molecules play a role in restricting DPSC attachment and migration to maintain DPSCs within their stem cell niche under steady-state conditions. These results may have implications for dental pulp development and regeneration.
KW - Adhesion
KW - Dental pulp stem cell
KW - Eph
KW - Ephrin
KW - MSC
KW - Migration
KW - Spreading
UR - http://www.scopus.com/inward/record.url?scp=33846025953&partnerID=8YFLogxK
U2 - 10.1634/stemcells.2006-0373
DO - 10.1634/stemcells.2006-0373
M3 - Article
C2 - 17204606
AN - SCOPUS:33846025953
SN - 1066-5099
VL - 25
SP - 156
EP - 164
JO - Stem Cells
JF - Stem Cells
IS - 1
ER -