EphB/ephrin-B interaction mediates adult stem cell attachment, spreading, and migration: implications for dental tissue repair.
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.
Stokowski
Agnieszka
A
Australian Research Council, Centre for the Molecular Genetics of Development, University of Adelaide, Adelaide, South Australia, Australia.
Shi
Songtao
S
Sun
Tao
T
Bartold
Peter Mark
PM
Koblar
Simon Andrea
SA
Gronthos
Stan
S
D000328:Adult; D001483:Base Sequence; D002448:Cell Adhesion; D002465:Cell Movement; D017931:DNA Primers; D003782:Dental Pulp / Q000166:cytology* / Q000502:physiology*; D036387:Ephrin-B1 / Q000502:physiology*; D036388:Ephrin-B2 / Q000502:physiology*; D006801:Humans; D007141:Immunoglobulin Fc Fragments / Q000494:pharmacology; D007074:Immunoglobulin G / Q000494:pharmacology; D007150:Immunohistochemistry; D016133:Polymerase Chain Reaction; D036081:Receptors, Eph Family / Q000502:physiology*; D011993:Recombinant Fusion Proteins / Q000494:pharmacology; D013234:Stem Cells / Q000166:cytology* / Q000502:physiology*; D014095:Tooth, Impacted / Q000601:surgery
D017931:DNA Primers; D036387:Ephrin-B1; D036388:Ephrin-B2; D007141:Immunoglobulin Fc Fragments; D007074:Immunoglobulin G; D011993:Recombinant Fusion Proteins; D036081:Receptors, Eph Family