title: The bone-forming effects of HIF-1α-transduced BMSCs promote osseointegration with dental implant in canine mandible.
abstract: The presence of insufficient bone volume remains a major clinical problem for dental implant placement to restore the oral function. Gene-transduced stem cells provide a promising approach for inducing bone regeneration and enhancing osseointegration in dental implants with tissue engineering technology. Our previous studies have demonstrated that the hypoxia-inducible factor-1α (HIF-1α) promotes osteogenesis in rat bone mesenchymal stem cells (BMSCs). In this study, the function of HIF-1α was validated for the first time in a preclinical large animal canine model in term of its ability to promote new bone formation in defects around implants as well as the osseointegration between tissue-engineered bone and dental implants. A lentiviral vector was constructed with the constitutively active form of HIF-1α (cHIF). The ectopic bone formation was evaluated in nude mice. The therapeutic potential of HIF-1α-overexpressing canine BMSCs in bone repair was evaluated in mesi-implant defects of immediate post-extraction implants in the canine mandible. HIF-1α mediated canine BMSCs significantly promoted new bone formation both subcutaneously and in mesi-implant defects, including increased bone volume, bone mineral density, trabecular thickness, and trabecular bone volume fraction. Furthermore, osseointegration was significantly enhanced by HIF-1α-overexpressing canine BMSCs. This study provides an important experimental evidence in a preclinical large animal model concerning to the potential applications of HIF-1α in promoting new bone formation as well as the osseointegration of immediate implantation for oral function restoration.
authors.affiliation: Ninth People's Hospital Affiliated with Shanghai Jiao Tong University, School of Medicine, Shanghai Key Laboratory of Stomatology, Shanghai, China.
authors.forename: Duohong
authors.initials: D
authors.lastname: Zou
authors.forename: Jiacai
authors.initials: J
authors.lastname: He
authors.forename: Kai
authors.initials: K
authors.lastname: Zhang
authors.forename: Jiewen
authors.initials: J
authors.lastname: Dai
authors.forename: Wenjie
authors.initials: W
authors.lastname: Zhang
authors.forename: Shaoyi
authors.initials: S
authors.lastname: Wang
authors.forename: Jian
authors.initials: J
authors.lastname: Zhou
authors.forename: Yuanliang
authors.initials: Y
authors.lastname: Huang
authors.forename: Zhiyuan
authors.initials: Z
authors.lastname: Zhang
authors.forename: Xinquan
authors.initials: X
authors.lastname: Jiang
mesh_terms: D000818:Animals; D015921:Dental Implants; D004285:Dogs; D015316:Genetic Therapy; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics*; D008297:Male; D008334:Mandible / Q000166:cytology / Q000502:physiology*; D059630:Mesenchymal Stem Cells / Q000378:metabolism*; D051379:Mice; D016348:Osseointegration / Q000235:genetics*; D010012:Osteogenesis / Q000235:genetics*; D023822:Tissue Engineering; D014161:Transduction, Genetic
chemical_list: D015921:Dental Implants; D051795:Hypoxia-Inducible Factor 1, alpha Subunit