Effect of Escherichia coli-produced recombinant human bone morphogenetic protein 2 on the regeneration of canine segmental ulnar defects
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 rege...
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| Veröffentlicht in: | Journal of bone and mineral metabolism 2012-07, Vol.30 (4), p.388-399 |
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| creator | Harada, Yasuji Itoi, Takamasa Wakitani, Shigeyuki Irie, Hiroyuki Sakamoto, Michiko Zhao, Dongwei Nezu, Yoshinori Yogo, Takuya Hara, Yasushi Tagawa, Masahiro |
| description | 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. |
| doi_str_mv | 10.1007/s00774-011-0329-x |
| format | Article |
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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.</description><identifier>ISSN: 0914-8779</identifier><identifier>EISSN: 1435-5604</identifier><identifier>DOI: 10.1007/s00774-011-0329-x</identifier><identifier>PMID: 22042292</identifier><language>eng</language><publisher>Japan: Springer Japan</publisher><subject>Animals ; Biocompatible Materials - chemistry ; Biocompatible Materials - therapeutic use ; Biological and medical sciences ; Bone Density - drug effects ; Bone Density Conservation Agents - administration & dosage ; Bone Density Conservation Agents - metabolism ; Bone Density Conservation Agents - therapeutic use ; Bone Morphogenetic Protein 2 - administration & dosage ; Bone Morphogenetic Protein 2 - biosynthesis ; Bone Morphogenetic Protein 2 - therapeutic use ; Bone Regeneration - drug effects ; Bone Resorption - prevention & control ; Bony Callus - drug effects ; Bony Callus - pathology ; Calcium Phosphates - chemistry ; Calcium Phosphates - therapeutic use ; Disease Models, Animal ; Diseases of the osteoarticular system ; Dogs ; Dose-Response Relationship, Drug ; Drug Delivery Systems ; Escherichia coli - metabolism ; Female ; Humans ; Implants, Experimental ; Indexing in process ; Medical sciences ; Medicine ; Medicine & Public Health ; Metabolic Diseases ; Original Article ; Orthopedics ; Recombinant Proteins - administration & dosage ; Recombinant Proteins - biosynthesis ; Recombinant Proteins - therapeutic use ; Ulna - drug effects ; Ulna - injuries ; Ulna - pathology ; Ulna Fractures - drug therapy ; Ulna Fractures - pathology ; Ulna Fractures - therapy</subject><ispartof>Journal of bone and mineral metabolism, 2012-07, Vol.30 (4), p.388-399</ispartof><rights>The Japanese Society for Bone and Mineral Research and Springer 2011</rights><rights>2015 INIST-CNRS</rights><rights>The Japanese Society for Bone and Mineral Research and Springer 2012</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c554t-720b0cb5774ed06dcde1c6949e79d0fac45aed26cd16fa5ae5d260f77a5ee9713</citedby><cites>FETCH-LOGICAL-c554t-720b0cb5774ed06dcde1c6949e79d0fac45aed26cd16fa5ae5d260f77a5ee9713</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s00774-011-0329-x$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s00774-011-0329-x$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,780,784,27915,27916,41479,42548,51310</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=26103279$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/22042292$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Harada, Yasuji</creatorcontrib><creatorcontrib>Itoi, Takamasa</creatorcontrib><creatorcontrib>Wakitani, Shigeyuki</creatorcontrib><creatorcontrib>Irie, Hiroyuki</creatorcontrib><creatorcontrib>Sakamoto, Michiko</creatorcontrib><creatorcontrib>Zhao, Dongwei</creatorcontrib><creatorcontrib>Nezu, Yoshinori</creatorcontrib><creatorcontrib>Yogo, Takuya</creatorcontrib><creatorcontrib>Hara, Yasushi</creatorcontrib><creatorcontrib>Tagawa, Masahiro</creatorcontrib><title>Effect of Escherichia coli-produced recombinant human bone morphogenetic protein 2 on the regeneration of canine segmental ulnar defects</title><title>Journal of bone and mineral metabolism</title><addtitle>J Bone Miner Metab</addtitle><addtitle>J Bone Miner Metab</addtitle><description>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.</description><subject>Animals</subject><subject>Biocompatible Materials - chemistry</subject><subject>Biocompatible Materials - therapeutic use</subject><subject>Biological and medical sciences</subject><subject>Bone Density - drug effects</subject><subject>Bone Density Conservation Agents - administration & dosage</subject><subject>Bone Density Conservation Agents - metabolism</subject><subject>Bone Density Conservation Agents - therapeutic use</subject><subject>Bone Morphogenetic Protein 2 - administration & dosage</subject><subject>Bone Morphogenetic Protein 2 - biosynthesis</subject><subject>Bone Morphogenetic Protein 2 - therapeutic use</subject><subject>Bone Regeneration - drug effects</subject><subject>Bone Resorption - prevention & control</subject><subject>Bony Callus - drug effects</subject><subject>Bony Callus - pathology</subject><subject>Calcium Phosphates - chemistry</subject><subject>Calcium Phosphates - therapeutic use</subject><subject>Disease Models, Animal</subject><subject>Diseases of the osteoarticular system</subject><subject>Dogs</subject><subject>Dose-Response Relationship, Drug</subject><subject>Drug Delivery Systems</subject><subject>Escherichia coli - metabolism</subject><subject>Female</subject><subject>Humans</subject><subject>Implants, Experimental</subject><subject>Indexing in process</subject><subject>Medical sciences</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>Metabolic Diseases</subject><subject>Original Article</subject><subject>Orthopedics</subject><subject>Recombinant Proteins - administration & dosage</subject><subject>Recombinant Proteins - biosynthesis</subject><subject>Recombinant Proteins - therapeutic use</subject><subject>Ulna - drug effects</subject><subject>Ulna - injuries</subject><subject>Ulna - pathology</subject><subject>Ulna Fractures - 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chemistry</topic><topic>Biocompatible Materials - therapeutic use</topic><topic>Biological and medical sciences</topic><topic>Bone Density - drug effects</topic><topic>Bone Density Conservation Agents - administration & dosage</topic><topic>Bone Density Conservation Agents - metabolism</topic><topic>Bone Density Conservation Agents - therapeutic use</topic><topic>Bone Morphogenetic Protein 2 - administration & dosage</topic><topic>Bone Morphogenetic Protein 2 - biosynthesis</topic><topic>Bone Morphogenetic Protein 2 - therapeutic use</topic><topic>Bone Regeneration - drug effects</topic><topic>Bone Resorption - prevention & control</topic><topic>Bony Callus - drug effects</topic><topic>Bony Callus - pathology</topic><topic>Calcium Phosphates - chemistry</topic><topic>Calcium Phosphates - therapeutic use</topic><topic>Disease Models, Animal</topic><topic>Diseases of the osteoarticular system</topic><topic>Dogs</topic><topic>Dose-Response Relationship, Drug</topic><topic>Drug Delivery Systems</topic><topic>Escherichia coli - metabolism</topic><topic>Female</topic><topic>Humans</topic><topic>Implants, Experimental</topic><topic>Indexing in process</topic><topic>Medical sciences</topic><topic>Medicine</topic><topic>Medicine & Public Health</topic><topic>Metabolic Diseases</topic><topic>Original Article</topic><topic>Orthopedics</topic><topic>Recombinant Proteins - administration & dosage</topic><topic>Recombinant Proteins - biosynthesis</topic><topic>Recombinant Proteins - therapeutic use</topic><topic>Ulna - drug effects</topic><topic>Ulna - injuries</topic><topic>Ulna - pathology</topic><topic>Ulna Fractures - drug therapy</topic><topic>Ulna Fractures - pathology</topic><topic>Ulna Fractures - therapy</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Harada, Yasuji</creatorcontrib><creatorcontrib>Itoi, Takamasa</creatorcontrib><creatorcontrib>Wakitani, Shigeyuki</creatorcontrib><creatorcontrib>Irie, Hiroyuki</creatorcontrib><creatorcontrib>Sakamoto, Michiko</creatorcontrib><creatorcontrib>Zhao, Dongwei</creatorcontrib><creatorcontrib>Nezu, Yoshinori</creatorcontrib><creatorcontrib>Yogo, Takuya</creatorcontrib><creatorcontrib>Hara, Yasushi</creatorcontrib><creatorcontrib>Tagawa, Masahiro</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Proquest Nursing & Allied Health Source</collection><collection>Health Medical collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni)</collection><collection>ProQuest Central</collection><collection>ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Nursing & Allied Health Premium</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Environmental Sciences and Pollution Management</collection><jtitle>Journal of bone and mineral metabolism</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Harada, Yasuji</au><au>Itoi, Takamasa</au><au>Wakitani, Shigeyuki</au><au>Irie, Hiroyuki</au><au>Sakamoto, Michiko</au><au>Zhao, Dongwei</au><au>Nezu, Yoshinori</au><au>Yogo, Takuya</au><au>Hara, Yasushi</au><au>Tagawa, Masahiro</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Effect of Escherichia coli-produced recombinant human bone morphogenetic protein 2 on the regeneration of canine segmental ulnar defects</atitle><jtitle>Journal of bone and mineral metabolism</jtitle><stitle>J Bone Miner Metab</stitle><addtitle>J Bone Miner Metab</addtitle><date>2012-07-01</date><risdate>2012</risdate><volume>30</volume><issue>4</issue><spage>388</spage><epage>399</epage><pages>388-399</pages><issn>0914-8779</issn><eissn>1435-5604</eissn><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.</abstract><cop>Japan</cop><pub>Springer Japan</pub><pmid>22042292</pmid><doi>10.1007/s00774-011-0329-x</doi><tpages>12</tpages></addata></record> |
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| ispartof | Journal of bone and mineral metabolism, 2012-07, Vol.30 (4), p.388-399 |
| issn | 0914-8779 1435-5604 |
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| subjects | Animals Biocompatible Materials - chemistry Biocompatible Materials - therapeutic use Biological and medical sciences Bone Density - drug effects Bone Density Conservation Agents - administration & dosage Bone Density Conservation Agents - metabolism Bone Density Conservation Agents - therapeutic use Bone Morphogenetic Protein 2 - administration & dosage Bone Morphogenetic Protein 2 - biosynthesis Bone Morphogenetic Protein 2 - therapeutic use Bone Regeneration - drug effects Bone Resorption - prevention & control Bony Callus - drug effects Bony Callus - pathology Calcium Phosphates - chemistry Calcium Phosphates - therapeutic use Disease Models, Animal Diseases of the osteoarticular system Dogs Dose-Response Relationship, Drug Drug Delivery Systems Escherichia coli - metabolism Female Humans Implants, Experimental Indexing in process Medical sciences Medicine Medicine & Public Health Metabolic Diseases Original Article Orthopedics Recombinant Proteins - administration & dosage Recombinant Proteins - biosynthesis Recombinant Proteins - therapeutic use Ulna - drug effects Ulna - injuries Ulna - pathology Ulna Fractures - drug therapy Ulna Fractures - pathology Ulna Fractures - therapy |
| title | Effect of Escherichia coli-produced recombinant human bone morphogenetic protein 2 on the regeneration of canine segmental ulnar defects |
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