Role Of Sonic Hedgehog Gene In Bone Defect Repair Around Dental Implant

Alveolar bone defects resulting from trauma, tumor, congenital deformities or serious periodontitis present a challenge to prosthetic reconstruction. The speed, quality and long-term stability of new bone formation in repair of alveolar bone defects are closely related to dental implantation. Autogenous bone, allograft bone, guided bone regeneration and other traditional methods for treatment of alveolar defects have achieved acceptable outcomes. However, the new generated bone can not be compared with the original bone. Gene-enhanced tissue engineering method as an alterative has attracted more and more attention. Bone metabolism is mainly mediated through local or systemic factors. Among these factors, Sonic hedgehog (Shh) is involved in osteoblast differentiation through BMP and PTHrP signal pathways, and may play an important role in bone formation. In this study, a gene-enhanced tissue-engineering approach was used to assess bone regenerative capacity of Sonic hedgehog (Shh)-transduced mesenchymal stem cells delivered to canine alveolar bone defects in beta-tricalcium phosphate (p-TCP) matrix. The lentiviral vector-mediated Shh gene (Lenti-Shh) was constructed in this study. Canine bone marrow-derived mesenchymal stem cells (MSCs) were transduced with the Lenti-Shh vector after routine isolation and culture in vitro. The exogenous Shh gene was assessed by the reverse transcriptase-polymerase chain reaction analysis and western blot detection. Osteogenic potential of Shh-transduced MSCs was evaluated in terms of the activity of alkaline phosphatase and the mRNA expression levels of osteogenic marker genes in vitro. Thereafter, the transduced MSCs were seeded on the biodegradableβ-TCP scaffold, and this composite was cultured in a three-dimensional culture system in vitro. The canine alveolar bone defects were surgically created following implant beds preparation in beagle dogs. Finally, the gene-enhanced tissue engineering bone was introduced into the alveolar defects around dental implants. The bone regenerative capacity of the gene-enhanced tissue engineering bone was assessed radiographically and histologically at 4 and 12 weeks postimplantation. The results showed that the increased bone formation accompanied with angiogenesis was induced by Shh transgene delivery in vivo. Quantitative analysis of histological sections confirmed statistically significant amounts of bone regeneration in Shh-enhanced groups compared to controls. Our study demonstrated that Shh gene delivery to bone defects, in this case through a gene-enhanced tissue-engineering approach, resulted in significant bone regeneration. This encourages further development of the Shh gene-enhanced tissue-engineering approach for bone regeneration.