Collagen-targeted BMP3 fusion proteins arrayed on collagen matrices or porous ceramics impregnated with Type I collagen enhance osteogenesis in a rat cranial defect model
| العنوان: | Collagen-targeted BMP3 fusion proteins arrayed on collagen matrices or porous ceramics impregnated with Type I collagen enhance osteogenesis in a rat cranial defect model |
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| المؤلفون: | Natalya Perelman, Edwin C. Shors, Marcel E. Nimni, Fredrick Hall, Baowei Tang, Bo Han |
| المصدر: | Journal of Orthopaedic Research. 20:747-755 |
| بيانات النشر: | Wiley, 2002. |
| سنة النشر: | 2002 |
| مصطلحات موضوعية: | Recombinant Fusion Proteins, medicine.medical_treatment, Bone Morphogenetic Protein 3, Calvaria, Bone morphogenetic protein, Bone morphogenetic protein 3, Collagen Type I, Extracellular matrix, Osteogenesis, medicine, Animals, Orthopedics and Sports Medicine, biology, Chemistry, Growth factor, Skull, Alkaline Phosphatase, Fusion protein, Rats, Inbred F344, Rats, Cell biology, Disease Models, Animal, Collagen, type I, alpha 1, medicine.anatomical_structure, Biochemistry, Bone Morphogenetic Proteins, biology.protein, Cell Division, Type I collagen |
| الوصف: | Bone morphogenetic protein 3 (BMP3) is a potent osteoinductive growth factor belonging to the TGF-beta superfamily. In this study, we engineered a recombinant BMP3 protein to include an auxiliary collagen-targeting domain derived from von Willebrand coagulation factor (vWF). The collagen-targeted BMP3 fusion protein (rhBMP3-C) was expressed in E. coli, purified from bacterial inclusion bodies, renatured under controlled redox conditions, and assayed for biological activity in vitro and in vivo. The renatured rhBMP3-C fusion protein bound tightly to collagen matrices and inhibited DNA synthesis in normal rat calvaria cells and in two out of three human osteosarcoma cell lines tested. Alkaline phosphatase activity was increased in rat calvarial cells and was decreased in osteosarcoma cells in vitro in a dose-dependent manner. Collagen sponges impregnated with rhBMP3-C and implanted subcutaneously in Fischer-344 rats induced dose-dependent dystrophic calcification of the collagen matrix, with no evidence of ectopic bone formation. However, local injection of rhBMP3-C infused in a collagen suspension induced new bone formation on the periosteal surface of rat calvaria. Finally, in a rat cranial defect model, surgical implantation of rhBMP3-C arrayed on either collagen sponges or on porous ceramics coated with Type I collagen exhibited marked osteoinductive properties. Taken together, these results demonstrate the feasibility of engineering and manufacturing targeted-BMPs which exhibit an integral gain-of-function that may be exploited to therapeutic advantage in (i) the enhancement of effective local concentrations, (ii) the prevention of systemic biodistribution and side effects, and (iii) the design of improved osteoinductive matrices. |
| تدمد: | 1554-527X 0736-0266 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::35ba436c126982e87a7e8ac400b13e1d https://doi.org/10.1016/s0736-0266(01)00157-7 |
| حقوق: | CLOSED |
| رقم الأكسشن: | edsair.doi.dedup.....35ba436c126982e87a7e8ac400b13e1d |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 1554527X 07360266 |
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