Hepatocyte growth factor is sequestered in dentine matrix and promotes regeneration-associated events in dental pulp cells

► HGF is sequestered in dentine matrix and solubilised by therapeutic pulp agents. ► HGF acts as a chemokine, inducing differentiation and mineralisation of pulp cells. ► HGF is likely important in signalling various aspects of dental pulp repair. Extracellular matrix of dentine contains a rich cocktail of soluble cytokines and growth factors which mediate wound repair of the dentine–pulp complex. Hepatocyte growth factor (HGF) is a mesenchyme derived growth factor regulating a broad range of physiological processes including tissue development and regeneration. In this study, we have investigated the sequestration of HGF in the dentine matrix and analysed its action as a chemokine in the induction of differentiation and mineral deposition in pulp derived cells in vitro. Using ELISA, the presence of HGF was demonstrated in solubilised fractions of dentine matrix released by the therapeutic pulp repair materials of white and grey mineral trioxide aggregate. HGF was shown to be a chemo-attractant for primary rat dental pulp cells (RDPCs) in transwell assays highlighting its potential in progenitor cell recruitment during dentine–pulp tissue repair. Transcription factors Osterix and Runx2, and genes encoding for Osteopontin and Osteocalcin, were up-regulated in HGF-exposed RDPC cultures compared with controls. Adenoviral-mediated expression of HGF in RDPCs or exposure to recombinant HGF induced mineral secretion in RDPCs which was significantly greater than controls. The receptor of HGF, c-Met was also detected within human dental pulp indicating the potential for HGF released from dentine matrix to contribute to cellular signalling events following tissue injury. Combined, these data suggest that HGF is important in the repair of the dentine–pulp complex potentially participating in several aspects of wound healing.