The role of SDF ‐1 and CXCR 4 on odontoblastic differentiation in human dental pulp cells

Aim To examine the role of stromal cell–derived factor 1 ( SDF ‐1) signalling during odontogenic differentiation in human dental pulp cells ( HDPC s). Methodology Human dental pulp cells were treated with differentiation medium, recombinant human SDF ‐1, neutralizing antibody for SDF ‐1 or CXCR 4, pertussis toxin ( PTX ) and AMD 3100. The expression of SDF ‐1 and its receptor chemokine receptor type 4 ( CXCR 4) was measured by reverse transcription–polymerase chain reaction ( RT ‐ PCR ) and Western blotting. Odontoblastic differentiation was determined using alkaline phosphatase ( ALP ) activity assay, mineralized nodule formation and marker mRNA s by RT ‐ PCR . Results Marked upregulation of SDF ‐1 and CXCR 4 mRNA and protein was observed in cells grown 7 days in osteogenic induction medium. The addition of recombinant human SDF ‐1 to HDPC s significantly ( P  < 0.05) increased ALP activity, mineralized nodule formation and odontoblast marker mRNA s in a dose‐dependent manner. Blocking SDF ‐1 signalling using antibodies against SDF ‐1 or CXCR 4, or the G ‐protein‐coupled receptor inhibitor PTX , and CXCR 4 inhibitor AMD 3100, strongly suppressed induction of odontogenic differentiation in HDPC s. Conclusions Odontoblastic differentiation was stimulated by SDF ‐1 activation and repressed by SDF ‐1/ CXCR 4 inhibition. Thus, SDF ‐1/ CXCR 4 signalling may be a new therapeutic target and strategy to promote repair and regeneration in endodontics.