title: Effect of Escherichia coli-produced recombinant human bone morphogenetic protein 2 on the regeneration of canine segmental ulnar defects.
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.
authors: Division of Veterinary Surgery, Nippon Veterinary and Life Science University, 1-7-1 Kyonan-cho, Musashino, Tokyo 180-8602, Japan. yasuji@nvlu.ac.jp
authors: Yasuji
authors: Y
authors: Harada
authors: Takamasa
authors: T
authors: Itoi
authors: Shigeyuki
authors: S
authors: Wakitani
authors: Hiroyuki
authors: H
authors: Irie
authors: Michiko
authors: M
authors: Sakamoto
authors: Dongwei
authors: D
authors: Zhao
authors: Yoshinori
authors: Y
authors: Nezu
authors: Takuya
authors: T
authors: Yogo
authors: Yasushi
authors: Y
authors: Hara
authors: Masahiro
authors: M
authors: Tagawa
mesh_terms: D000818:Animals; D001672:Biocompatible Materials / Q000737:chemistry / Q000627:therapeutic use; D015519:Bone Density / Q000187:drug effects; D050071:Bone Density Conservation Agents / Q000008:administration & dosage / Q000378:metabolism / Q000627:therapeutic use*; D055396:Bone Morphogenetic Protein 2 / Q000008:administration & dosage / Q000096:biosynthesis / Q000627:therapeutic use*; D001861:Bone Regeneration / Q000187:drug effects*; D001862:Bone Resorption / Q000517:prevention & control; D002146:Bony Callus / Q000187:drug effects / Q000473:pathology; D002130:Calcium Phosphates / Q000737:chemistry / Q000627:therapeutic use; D004195:Disease Models, Animal; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D016503:Drug Delivery Systems; D004926:Escherichia coli / Q000378:metabolism*; D005260:Female; D006801:Humans; D020007:Implants, Experimental; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000096:biosynthesis / Q000627:therapeutic use; D014457:Ulna / Q000187:drug effects* / Q000293:injuries / Q000473:pathology; D014458:Ulna Fractures / Q000188:drug therapy* / Q000473:pathology / Q000628:therapy
chemical_list: C525718:BMP2 protein, human; D001672:Biocompatible Materials; D050071:Bone Density Conservation Agents; D055396:Bone Morphogenetic Protein 2; D002130:Calcium Phosphates; D011994:Recombinant Proteins; C485817:beta-tricalcium phosphate