Damage to the dentin matrix instigates the proliferation and mobilization of dental progenitor cells to the injury site, the mechanisms of which are not defined. EphB receptors and ephrin-B ligands expressed within the perivascular niche of dental pulp have been implicated following tooth injury. We propose that elevated levels of ephrin-B1 following injury may prevent the proliferation and migration of dental pulp stem cell (DPSC), while EphB/ephrin-B interaction facilitates odontoblastic differentiation. The migration, proliferation, and differentiation of DPSC in response to Eph/ephrin-B molecules was assessed in an established ex vivo tooth injury model and by in vitro assays for the assessment of colony formation and differentiation. Analysis of our data demonstrated that EphB forward signaling promoted DPSC proliferation, while inhibiting migration. Conversely, reverse signaling enhanced DPSC mineral production. These observations suggest that EphB/ephrin-B molecules are important for perivascular DPSC migration toward the dentin surfaces and differentiation into functional odontoblasts, following damage to the dentin matrix.
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