Abstract:

BACKGROUND: Although recent studies have shown that the local gene therapy can promote the formation of new bone in distraction gap, the effect of gene therapy on the expression of local growth factors is unclear.
OBJECTIVE: To investigate the effect of electroporation-mediated gene therapy on the expression of transforming growth factor-β1 (TGF-β1) during mandibular distraction osteogenesis in a rabbit model.
METHODS: Mandibular distraction of 0.8 mm/d was performed in New-Zealand rabbits at 3 days after bilateral mandibular osteotomy and lasted for 7 days. After the completion of distraction, the rabbits were randomly divided into five groups. 2 μg      (0.1 μg/μL) recombinant plasmid pIRES-hVEGF165-hBMP2, pIRES-hBMP2, pIRES-hVEGF165, pIRES and normal saline was injected into the distraction area respectively. After injection, every group employed electroporation.
RESULTS AND CONCLUSION: Immunohistochemical staining showed that TGF-β1 was mainly expressed in the cytoplasm. Seven days after transfection, the staining of TGF-β1 was positive on osteocytes of bone edge, osteocytes of woven bone callus and osteoblasts on the surface of bone callus. At 14 days, the expression of TGF-β1 was found on osteocytes of newborn woven bone callus, osteoblasts on the surface of bone callus, stromal cells in granulation tissue, mononuclear giant cells and multinucleated giant cells. At 28 days, the positive expression of TGF-β1 was decreased obviously. Compared with the injection of pIRES and normal saline, the expression of TGF-β1 was significantly higher after the injection of recombinant plasmid pIRES-hVEGF165-hBMP2, pIRES-hBMP2 and pIRES-hVEGF165 (P < 0.05 or P < 0.01). It suggests that gene therapy can promote TGF-β1 expression effectively and promote the formation of new bone and cell matrix in distraction gap.