The induction of bone formation in rat calvarial defects and subcutaneous tissues by recombinant human BMP-2, produced in Escherichia coli.
We investigated the ability of recombinant human bone morphogenetic protein-2, produced from Escherichia coli (ErhBMP-2), to form orthotopic and ectopic bone in rat models. BMP-2 was expressed in E. coli and extracted from the inclusion bodies. Critical-sized calvarial defects and subcutaneous pouches were created in rats, and an absorbable collagen sponge (ACS) was loaded with different doses of ErhBMP-2 for implantation. ACS alone and sham surgery controls were also included. Implant sites were evaluated by histological and/or histometric analyses following a 2- or 8-week healing interval. In the calvarial defect model, enhanced bone formation was observed with all doses of ErhBMP-2, while only limited amounts of new bone were found in controls. In the ectopic subcutaneous implant model, bone formation was clearly observed in all animals treated with ErhBMP-2 at 2 weeks. However, at 8 weeks, less new bone formation was detected than at 2 weeks. Nevertheless, the remaining new bone showed an advanced degree of bone remodeling and more maturity than that observed at 2 weeks. These results showed that ErhBMP-2 was osteoinductive under controlled in vivo conditions. Thus, ErhBMP-2 has definite potential as an alternative to rhBMP-2 produced in a eukaryotic system for clinical use.
Department of Dentistry, Hangang Secred Heart Hospital, College of Medicine, Hallym University 94-195 Youngdeungpo-dong, Youngdeungpo-gu, Seoul 150030, Republic of Korea.
Ji-Hyun
JH
Lee
Chang-Sung
CS
Kim
Kyung-Hee
KH
Choi
Ui-Won
UW
Jung
Jeong-Ho
JH
Yun
Seong-Ho
SH
Choi
Kyoo-Sung
KS
Cho
D000818:Animals; D001846:Bone Development / Q000187:drug effects*; D055396:Bone Morphogenetic Protein 2 / Q000235:genetics / Q000494:pharmacology*; D004926:Escherichia coli / Q000235:genetics*; D006801:Humans; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000235:genetics / Q000494:pharmacology; D012886:Skull / Q000002:abnormalities*; D050151:Subcutaneous Fat / Q000187:drug effects*
D055396:Bone Morphogenetic Protein 2; D011994:Recombinant Proteins