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The bone-forming effects of HIF-1α-transduced BMSCs promote osseointegration with dental implant in canine mandible.

Zou D, He J, Zhang K, Dai J, Zhang W, Wang S, Zhou J, Huang Y, Zhang Z, Jiang X - PLoS ONE (2012)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Ninth People's Hospital Affiliated with Shanghai Jiao Tong University, School of Medicine, Shanghai Key Laboratory of Stomatology, Shanghai, China.

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.

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Characterization of F344 canine BMSCs and target gene transduction.Flow cytometry analysis of cell surface markers CD90, CD105, CD31, and CD34 (A); A multiplicity of infection of 7 pfu/cell achieved high transfer efficiency, around 90%, 4 days after Lenti-GFP, Lenti-HIF, and cHIF transduction of canine BMSCs (100×) (B).
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pone-0032355-g001: Characterization of F344 canine BMSCs and target gene transduction.Flow cytometry analysis of cell surface markers CD90, CD105, CD31, and CD34 (A); A multiplicity of infection of 7 pfu/cell achieved high transfer efficiency, around 90%, 4 days after Lenti-GFP, Lenti-HIF, and cHIF transduction of canine BMSCs (100×) (B).

Mentions: At passage 3, BMSCs were characterized by flow cytometry. CD90 and CD105 were highly expressed, whereas CD31 and CD34 were rarely detected (Figure 1A). Under an optimal multiplicity of infection (MOI = 7), BMSCs were transduced by Lenti-GFP, Lenti-HIF, and Lenti-cHIF. Four days after transduction, BMSCs fluoresced green under inverted fluorescence microscopy, showing efficiency of transduction of approximately 90% (Figure 1B). HIF-1α mRNA and protein expression was up-regulated in the target gene groups compared with the control group by qPCR and western blotting, respectively (Figure 2).


The bone-forming effects of HIF-1α-transduced BMSCs promote osseointegration with dental implant in canine mandible.

Zou D, He J, Zhang K, Dai J, Zhang W, Wang S, Zhou J, Huang Y, Zhang Z, Jiang X - PLoS ONE (2012)

Characterization of F344 canine BMSCs and target gene transduction.Flow cytometry analysis of cell surface markers CD90, CD105, CD31, and CD34 (A); A multiplicity of infection of 7 pfu/cell achieved high transfer efficiency, around 90%, 4 days after Lenti-GFP, Lenti-HIF, and cHIF transduction of canine BMSCs (100×) (B).
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3293808&req=5

pone-0032355-g001: Characterization of F344 canine BMSCs and target gene transduction.Flow cytometry analysis of cell surface markers CD90, CD105, CD31, and CD34 (A); A multiplicity of infection of 7 pfu/cell achieved high transfer efficiency, around 90%, 4 days after Lenti-GFP, Lenti-HIF, and cHIF transduction of canine BMSCs (100×) (B).
Mentions: At passage 3, BMSCs were characterized by flow cytometry. CD90 and CD105 were highly expressed, whereas CD31 and CD34 were rarely detected (Figure 1A). Under an optimal multiplicity of infection (MOI = 7), BMSCs were transduced by Lenti-GFP, Lenti-HIF, and Lenti-cHIF. Four days after transduction, BMSCs fluoresced green under inverted fluorescence microscopy, showing efficiency of transduction of approximately 90% (Figure 1B). HIF-1α mRNA and protein expression was up-regulated in the target gene groups compared with the control group by qPCR and western blotting, respectively (Figure 2).

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Ninth People's Hospital Affiliated with Shanghai Jiao Tong University, School of Medicine, Shanghai Key Laboratory of Stomatology, Shanghai, China.

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.

Show MeSH
Related in: MedlinePlus