Abstract: Objective To observe the effect of nerve growth factor (NGF) combined with dental pulp stem cells (DPSCs) on peri-implant osseointegration in rats and explore the underlying mechanism. Methods Cultured DPSCs were treated with NFG or with NFG plus the TrkA antagonist K252a, and after osteogenic induction, the formation of calcium nodules was observed andthe expressions of RUNX2 and osteocalcin (OCN) were detected with Western blotting. SD rat models with femoral implantation of dental implants were established and divided into control, DPSCs, DPSCs+NGF, DPSCs+K252a, and DPSCs+NGF+K252a groups, and in all but the control group, DPSCs were injected locally before placement of the implants (n=8); NGF, K252a and their combination were injected intraperitoneally on a daily basis for 4 weeks. All the rats underwent micro-CT, and the peri-implant bone tissues were collected for HE staining and detection of RUNX2 and OCN expressions using Western blotting. Results In cultured DPSCs, the number of calcium nodules and the expression levels of RUNX2 and OCN were significantly higher in NGF group than in the control group (P<0.05), and were significantly lower in NGF+K252a group than in NGF group (P<0.05). In the rat models, the BMD, TB. Th, TB. N and expressions of RUNX2 and OCN in the peri-implant bone tissues were significantly higher in DPSCs group and DPSCs+NGF group than in the control group (P<0.05), significantly higher in DPSCs+NGF group than in DPSCs group (P<0.05), comparable between DPSCs+K252a group and DPSCs group (P> 0.05), and significantly lower in DPSCs+NGF+K252a group than in DPSCs+NGF group (P<0.05). Conclusion NGF combined with DPSCs can promote osseointegration in the peri-implant tissues in rats possibly due to a TrkA-mediated effect of NGF for promoting osteogenic differentiation of the DPSCs.

Key words: dental pulp stem cells; nerve growth factor; implant; osseointegration; osteogenic differentiation