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Percutaneous Nonviral Delivery of Hepatocyte Growth Factor in an Osteotomy Gap Promotes Bone Repair in Rabbits: A Preliminary Study

  • Symposium: Advances in Limb Lengthening and Reconstruction
  • Published:
Clinical Orthopaedics and Related Research

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.

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Acknowledgments

We thank Yoh Zen, MD, PhD, Department of Pathology, Kanazawa University, for assistance in the histologic examination. Anges MG Inc (Tokyo, Japan) kindly supplied the hHGF expression vector.

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Authors and Affiliations

  1. Department of Orthopaedic Surgery, Graduate School of Medical Science, Kanazawa University, 13-1 Takara-machi, Kanazawa, 920-8641, Japan

    Hidenori Matsubara MD, Hiroyuki Tsuchiya MD, PhD, Koji Watanabe MD, PhD, Akihiko Takeuchi MD, PhD & Katsuro Tomita MD, PhD

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  1. Hidenori Matsubara MD
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  2. Hiroyuki Tsuchiya MD, PhD
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  3. Koji Watanabe MD, PhD
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  4. Akihiko Takeuchi MD, PhD
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  5. Katsuro Tomita MD, PhD
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Correspondence to Hiroyuki Tsuchiya MD, PhD.

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Each author certifies that he or she has no commercial associations (eg, consultancies, stock ownership, equity interest, patent/licensing arrangements, etc) that might pose a conflict of interest in connection with the submitted article.

Each author certifies that his or her institution has approved the animal protocol for this investigation and that all investigations were conducted in conformity with ethical principles of research.

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Matsubara, H., Tsuchiya, H., Watanabe, K. et al. Percutaneous Nonviral Delivery of Hepatocyte Growth Factor in an Osteotomy Gap Promotes Bone Repair in Rabbits: A Preliminary Study. Clin Orthop Relat Res 466, 2962–2972 (2008). https://doi.org/10.1007/s11999-008-0493-z

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  • DOI: https://doi.org/10.1007/s11999-008-0493-z

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