Bone regeneration properties of granulocyte colony-stimulating factor via neovascularization and osteogenesis.
OBJECTIVE
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Ishida
Kazunari
K
Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine, Kobe, Japan.
Matsumoto
Tomoyuki
T
Sasaki
Ken
K
Mifune
Yutaka
Y
Tei
Katsumasa
K
Kubo
Seiji
S
Matsushita
Takehiko
T
Takayama
Koji
K
Akisue
Toshihiro
T
Tabata
Yasuhiko
Y
Kurosaka
Masahiro
M
Kuroda
Ryosuke
R
D000818:Animals; D001861:Bone Regeneration / Q000187:drug effects* / Q000235:genetics; D002478:Cells, Cultured; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D016179:Granulocyte Colony-Stimulating Factor / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology; D007150:Immunohistochemistry; D018919:Neovascularization, Physiologic / Q000187:drug effects* / Q000235:genetics; D010012:Osteogenesis / Q000187:drug effects / Q000235:genetics*; D011817:Rabbits; D016188:Receptors, Granulocyte Colony-Stimulating Factor / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction
D016188:Receptors, Granulocyte Colony-Stimulating Factor; D016179:Granulocyte Colony-Stimulating Factor