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Effect of Escherichia coli-produced recombinant human bone morphogenetic protein 2 on the regeneration of canine segmental ulnar defects

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Abstract

Because bone morphogenetic protein 2 gene transfected Escherichia coli (E-BMP-2) produce recombinant human BMP-2 (rhBMP-2) more efficiently than mammalian cells (Chinese hamster ovary [CHO]-BMP-2), they may be a more cost-effective source of rhBMP-2 for clinical use. However, use of E-BMP-2 for regenerating long bones in large animals has not been reported. In the current study, we evaluated the healing efficacy of E-BMP-2 in a canine model. We created 2.5-cm critical-size segmental ulnar defects in test animals, then implanted E-BMP-2 and 700 mg of artificial bone (beta-tricalcium phosphate; β-TCP) into the wounds. We examined the differential effects of 5 E-BMP-2 treatments (0, 35, 140, 560, and 2240 μg) across 5 experimental groups (control, BMP35, BMP140, BMP560, and BMP2240). Radiography and computed tomography were used to observe the regeneration process. The groups in which higher doses of E-BMP-2 were administered (BMP560 and BMP2240) displayed more pronounced bone regeneration; the regenerated tissues connected to the host bone, and the cross-sectional areas of the regenerated bone were larger than those of the originals. The groups in which lower doses of E-BMP-2 were administered (BMP35 and BMP140) experienced relatively less bone regeneration; furthermore, the regenerated tissues failed to connect to the host bone. In these groups, the cross-sectional areas of the regenerated bone were equal to or smaller than those of the originals. No regeneration was observed in the control group. These findings suggest that, like CHO-BMP-2, E-BMP-2 can be used for the regeneration of large defects in long bones and that its clinical use might decrease the cost of bone regeneration treatments.

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Acknowledgments

This work was partially supported by the 2008 Strategic Research Base Development Program for Private Universities from the Ministry of Education, Culture, Sports, Science and Technology of Japan (MEXT).

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Authors and Affiliations

  1. Division of Veterinary Surgery, Nippon Veterinary and Life Science University, 1-7-1 Kyonan-cho, Musashino, Tokyo, 180-8602, Japan

    Yasuji Harada, Takamasa Itoi, Yoshinori Nezu, Takuya Yogo, Yasushi Hara & Masahiro Tagawa

  2. Department of Orthopaedic Surgery, Osaka City University Graduate School of Medicine, 1-4-3 Asahi-machi, Abeno-ku, Osaka, 545-8585, Japan

    Shigeyuki Wakitani

  3. Osteopharma Inc., YSK Bldg. 2F, 1-2-5 Uchi-hommachi, Chuo-ku, Osaka, 540-0026, Japan

    Hiroyuki Irie

  4. Hoya Corporation, 1-1-110 Tsutsujigaoka, Akishima, Tokyo, 196-0012, Japan

    Michiko Sakamoto

  5. Animal Disease Prevention and Prophylaxis Research Center, Nippon Veterinary and Life Science University, 1-7-1 Kyonan-cho, Musashino, Tokyo, 180-8602, Japan

    Dongwei Zhao

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  1. Yasuji Harada
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  2. Takamasa Itoi
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  9. Yasushi Hara
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  10. Masahiro Tagawa
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Correspondence to Yasuji Harada.

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Harada, Y., Itoi, T., Wakitani, S. et al. Effect of Escherichia coli-produced recombinant human bone morphogenetic protein 2 on the regeneration of canine segmental ulnar defects. J Bone Miner Metab 30, 388–399 (2012). https://doi.org/10.1007/s00774-011-0329-x

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  • DOI: https://doi.org/10.1007/s00774-011-0329-x

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