VEGF Modulates Angiogenesis and Osteogenesis in Shockwave-Promoted Fracture Healing in Rabbits

Wang, Ching-Jen; Huang, Ko-En; Sun, Yi-Chih; Yang, Ya-Ju; Ko, Jih-Yang; Weng, Lin-Hsiu; Wang, Feng-Sheng

doi:10.1016/j.jss.2010.01.045

« Previous Next »Journal of Surgical Research
Volume 171, Issue 1 , Pages 114-119, November 2011

VEGF Modulates Angiogenesis and Osteogenesis in Shockwave-Promoted Fracture Healing in Rabbits

Ching-Jen Wang, M.D.
- Department of Orthopedic Surgery, Chang Gung University College of Medicine, Chang Gung Memorial Hospital-Kaohsiung Medical Center Kaohsiung, Taiwan
- To whom correspondence and reprint requests should be addressed at Department of Orthopedic Surgery, Chang Gung Memorial Hospital-Kaohsiung Medical Center, 123 Ta-Pei Road, Niao-Sung Hsing, Kaohsiung, Taiwan 833.
Ko-En Huang, M.D.
- Department of Obstetrics and Gynecology, Chang Gung University College of Medicine, Chang Gung Memorial Hospital-Kaohsiung Medical Center Kaohsiung, Taiwan
Yi-Chih Sun, B.A.
- Department of Medical Research, Chang Gung University College of Medicine, Chang Gung Memorial Hospital-Kaohsiung Medical Center Kaohsiung, Taiwan
Ya-Ju Yang, B.A.
- Department of Medical Research, Chang Gung University College of Medicine, Chang Gung Memorial Hospital-Kaohsiung Medical Center Kaohsiung, Taiwan
Jih-Yang Ko, M.D.
- Department of Orthopedic Surgery, Chang Gung University College of Medicine, Chang Gung Memorial Hospital-Kaohsiung Medical Center Kaohsiung, Taiwan
Lin-Hsiu Weng, M.D.
- Department of Orthopedic Surgery, Chang Gung University College of Medicine, Chang Gung Memorial Hospital-Kaohsiung Medical Center Kaohsiung, Taiwan
Feng-Sheng Wang, Ph.D.
- Department of Medical Research, Chang Gung University College of Medicine, Chang Gung Memorial Hospital-Kaohsiung Medical Center Kaohsiung, Taiwan

Received 18 November 2009 published online 22 February 2010.

Objective

Strong vascular endothelial growth factor (VEGF) expression of osteoprogenitors was found in callus site during fracture healing. The aim of this study was to investigate whether VEGF modulates the angiogenesis and osteogenesis in shockwave-promoted fracture healing in rabbits.

Materials and Methods

Twenty-seven Japanese rabbits were used in the study. A fracture of left tibia with 5 mm gap was created, and the fracture was stabilized with an external fixator. The rabbits were randomly divided into three groups. Group I was the control group and received no shockwave therapy. Group II received shockwave therapy, and group III was pretreated with bevacizumab, a monoclonal antibody against VEGF, before receiving shockwave. Radiographs of the tibia were obtained at 1, 4, and 8 wk. Bone mineral density was performed at 8 wk. The rabbits were euthanized at 8 wk, and the bone specimens were subjected to histomorphological examination and immunohistochemical analysis.

Results

At 8 wk, radiographs showed considerably better bone healing and remodeling of the fracture in group II compared with groups I and III, whereas no discernable difference was noted between group I and group III. The BMD values were significantly higher in group II than groups I and III, but no difference noted between group I and group III. In histomorphological examination, significant increases in bone tissue was were noted in group II compared with groups I and III, but no difference was noted between group I and group III. In immunohistochemical analysis, significant increases in VEGF, vWF, PCNA, BMP-2 and osteocalcin, and a decrease in TUNEL expression were observed in group II compared with groups I and III, but no statistical difference was noted between group I and group III.

Conclusion

Significant increases in VEGF and angiogenic and osteogenic growth factors were noted in shockwave-promoted bone healing. Pre-treatment with bevacizumab inhibited VEGF and in turn, attenuated the effect of shockwave. It appears that VEGF modulates angiogenesis and osteogenesis in shockwave-promoted bone healing in rabbits.

Key Words: VEGF, angiogenesis, osteogenesis, fracture, shockwave