Bone Regeneration Properties of Granulocyte Colony-Stimulating Factor via Neovascularization and Osteogenesis

Abstract

It has been well recognized that appropriate vascularization is emerging as a prerequisite for bone development and regeneration. The aim of this study was to test the hypothesis that locally applied granulocyte colony-stimulating factor (G-CSF) enhances bone regeneration via revascularization and osteogenesis. A segmental bone defect (20mm) was created at the diaphysis of the rabbit ulna. The defects were treated with cationized gelatin hydrogel, which was the drug delivery system, with G-CSF, and then bone regeneration, neovascularization, and osteogenesis properties with G-CSF were assessed. Radiographic, computed tomography, and histological findings revealed that bone formation was significantly promoted in G-CSF-treated group as early as 2 weeks. Immunohistochemistry, real-time reverse transcription-polymerase chain reaction, and flow cytometry studies indicated that angiogenesis/vasculogenesis, which are regulated by mobilization and incorporation of CD34+/G-CSF receptor (CSFR+) cells, and osteogenesis, which is regulated by osteocalcin+/G-CSFR+ cells, were also significantly enhanced in the G-CSF group. This study suggests that locally applied G-CSF contributes to an ideal local environment for fracture healing by supplying adequate blood flow and stimulating osteogenesis. G-CSF may have the therapeutic potential for bone regeneration.