The role of SDF-1 and CXCR4 on odontoblastic differentiation in human dental pulp cells

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Abstract

Aim

To examine the role of stromal cell–derived factor 1 (SDF-1) signalling during odontogenic differentiation in human dental pulp cells (HDPCs).

Methodology

Human dental pulp cells were treated with differentiation medium, recombinant human SDF-1, neutralizing antibody for SDF-1 or CXCR4, pertussis toxin (PTX) and AMD3100. The expression of SDF-1 and its receptor chemokine receptor type 4 (CXCR4) 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 mRNAs by RT-PCR.

Results

Marked upregulation of SDF-1 and CXCR4 mRNA and protein was observed in cells grown 7 days in osteogenic induction medium. The addition of recombinant human SDF-1 to HDPCs significantly (P < 0.05) increased ALP activity, mineralized nodule formation and odontoblast marker mRNAs in a dose-dependent manner. Blocking SDF-1 signalling using antibodies against SDF-1 or CXCR4, or the G-protein-coupled receptor inhibitor PTX, and CXCR4 inhibitor AMD3100, strongly suppressed induction of odontogenic differentiation in HDPCs.

Conclusions

Odontoblastic differentiation was stimulated by SDF-1 activation and repressed by SDF-1/CXCR4 inhibition. Thus, SDF-1/CXCR4 signalling may be a new therapeutic target and strategy to promote repair and regeneration in endodontics.

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