Journal List > J Korean Orthop Assoc > v.46(5) > 1013093

Shin, Lee, Lee, Kim, Yoo, Cho, and Choi: Enhancement of Vasculogenesis and Osteogenesis Using Granulocyte-Colony Stimulating Factor in the Rat Model of Tibial Distraction Osteogenesis

Abstract

Purpose

Proper speed of distraction is critical for successful new bone formation in distraction osteogenesis. The purpose of this study was to evaluate the effect of granulocyte-colony stimulating factor (G-CSF) on formation of new blood vessels and new bones in the rat model of tibial distraction osteogenesis (DO) to develop enhancement method of bone formation while increasing the distraction speed.

Materials and Methods

Forty two rat-tibial DO models were included in this study, and were divided into 3 groups; group I (rapid distraction), group II (rapid distraction with G-CSF), and group III (slow distraction). The amount of bone formation and relative blood flow were analyzed by sequential radiographs and laser Doppler perfusion imaging (LDPI). Blood sampling was done before G-CSF injection, at 2 weeks and 5 weeks after G-CSF injection and surface expression such as Scal-1+ and C-kit+ of endothelial progenitor cells (EPCs) was analyzed by fluorescence-activated cell sorter (FACS) for the effects of G-CSF in inducing mobilization of EPCs.

Results

The amount of new bone formation in the distraction gap on serial radiographs was higher during the consolidation period in groups II and III than in group I but, the difference was not significant (p>0.05). The relative blood flow in the distraction gap in groups II and III increased more significantly than in group I (p<0.05). FACS analysis showed an increased EPCs fraction after G-CSF injection.

Conclusion

We demonstrated that G-CSF administration ameliorated bone formation and blood flow during rapid distraction in the rat model of tibial distraction osteogenesis. We think that G-CSF has an effect on mobilization of EPCs resulting in an increase in the blood flow.

Figures and Tables

Figure 1
This photo shows bilateral mono-fixators at the right tibia in rat DO (distraction ostegenesis) model.
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Figure 2
Serial radiographs during consolidation period in groups 1 (A), 2 (B), and 3 (C).
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Figure 3
This graph shows average of relative bone density value during consolidation period after cessation of distraction in 3 groups. Relative bone densities of groups 2, and 3 were higher than that of group 1 during 6 weeks and that was not statistically significant (p>0.05, by student t-test).
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Figure 4
This graph shows average of relative blood flow after operation (corticotomy) in 3 groups. Relative blood flows of groups 2, and 3 were higher than that of group 1 during 6 weeks and that was statistically significant (*p=0.04, p=0.03, by student t-test).
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Figure 5
G-CSF induced the mobilization of Sca-1 and C-kit positive cell fractions (right shift in FACS analysis, solid line) before the start of distraction (dash line). Sca-1 and C-kit positive cell fractions maintained during distraction and it decreased after 3 weeks of consolidation.
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