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TISSUE-SPECIFIC STEM CELLS

EphB/Ephrin-B Interaction Mediates Adult Stem Cell Attachment, Spreading, and Migration: Implications for Dental Tissue Repair

^aAustralian Research Council, Centre for the Molecular Genetics of Development,
^bSchool of Molecular and Biomedical Science (Genetics), and
^eColgate Australian Clinical Dental Research Centre, Dental School, University of Adelaide, Adelaide, South Australia, Australia;
^cMesenchymal Stem Cell Group, Division of Haematology, Institute of Medical and Veterinary Science, Hanson Institute, Adelaide, South Australia, Australia;
^dSchool of Dentistry, University of Southern California, Los Angeles, California, USA

Key Words. Eph • Ephrin • MSC • Dental pulp stem cell • Migration • Adhesion • Spreading

Correspondence: Stan Gronthos, B.Sc., M.Sc., Ph.D., Mesenchymal Stem Cell Group, Division of Haematology, Institute of Medical and Veterinary Science, Frome Road, Adelaide 5000, South Australia, Australia. Telephone: 61-8-8222-3460; Fax: 61-8-8222-3139; e-mail: stan.gronthos{at}imvs.sa.gov.au

Received June 20, 2006; accepted for publication September 20, 2006.


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.

This article has been cited by other articles:

				A. Arthur, G. Rychkov, S. Shi, S. A. Koblar, and S. Gronthos Adult Human Dental Pulp Stem Cells Differentiate Toward Functionally Active Neurons Under Appropriate Environmental Cues Stem Cells, July 1, 2008; 26(7): 1787 - 1795. [Abstract] [Full Text] [PDF]