Percutaneous nonviral delivery of hepatocyte growth factor in an osteotomy gap promotes bone repair in rabbits: a preliminary study.

Abstract

Hepatocyte growth factor (HGF) was initially identified in cultured hepatocytes and subsequently reported to induce angiogenic, morphogenic, and antiapoptotic activity in various tissues. These properties suggest a potential influence of HGF on bone healing. We asked if gene transfer of human HGF (hHGF) into an osteotomy gap with a hemagglutinating virus of Japan-envelope (HVJ-E) vector promotes bone healing in rabbits. HVJ-E that contained either hHGF or control plasmid was percutaneously injected into the osteotomy gap of rabbit tibias on Day 14. The osteotomy gap was evaluated by radiography, pQCT, mechanical tests, and histology at Week 8. The expression of hHGF was evaluated by reverse transcriptase-polymerase chain reaction and immunohistochemistry at Week 3. Radiography, pQCT, and histology suggested the hHGF group had faster fracture healing. Mechanical tests demonstrated the hHGF group had greater mechanical strength. The injected tissues at 3 weeks expressed hHGF mRNA by reverse transcriptase-polymerase chain reaction. hHGF-positive immunohistochemical staining was observed in various cells at the osteotomy gap at Week 3. The data suggest delivery of hHGF plasmid into the osteotomy gap promotes fracture repair, and HGF could become a novel agent for fracture treatment.