title: Non-glycosylated BMP-2 can induce ectopic bone formation at lower concentrations compared to glycosylated BMP-2.
abstract: Bone morphogenic protein-2 (BMP-2) is a well-known growth factor that can improve the biological performance of bone substitute materials. BMP-2 produced via bacterial expression systems are non-glycosylated (ng) whereas native and recombinant equivalents produced in mammalian cell expression systems are glycosylated (g) proteins. ngBMP-2 is less soluble, resulting in lower BMP-2 release from carriers as used as bone substitute materials. This seems promising for reducing the amount of included growth factor in bone substitute materials. Hence, it was hypothesized that ngBMP-2 would induce formation of the same amount of bone at an ectopic site at lower dosage as gBMP-2. To that end, gBMP-2 and ngBMP-2 were firstly in vitro comparatively evaluated for biological activity and release from a calcium phosphate (CaP) based bone substitute material. Thereafter, an ectopic implantation model in rats was used, in which gBMP-2 and ngBMP2 were loaded in various dosages (2-20 μg/implant) on the CaP-based bone substitute material and implanted for 4 and 12 weeks. The results revealed that both the in vitro biological activity of and the in vitro release of ngBMP-2 are lower compared to gBMP2. Upon ectopic implantation, however, ngBMP-2 loaded implants induced more bone formation at lower concentrations from 4-weeks onward compared to gBMP-2 equivalents, indicating the value of ngBMP-2 as a potential alternative for mammalian produced recombinant BMP-2 for bone regenerative therapies.
authors.affiliation: Department of Biomaterials, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands.
authors.forename: F C J
authors.initials: FC
authors.lastname: van de Watering
authors.forename: J J J P
authors.initials: JJ
authors.lastname: van den Beucken
authors.forename: S P
authors.initials: SP
authors.lastname: van der Woning
authors.forename: A
authors.initials: A
authors.lastname: Briest
authors.forename: A
authors.initials: A
authors.lastname: Eek
authors.forename: H
authors.initials: H
authors.lastname: Qureshi
authors.forename: L
authors.initials: L
authors.lastname: Winnubst
authors.forename: O C
authors.initials: OC
authors.lastname: Boerman
authors.forename: J A
authors.initials: JA
authors.lastname: Jansen
mesh_terms: D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology / Q000187:drug effects; D055396:Bone Morphogenetic Protein 2 / Q000494:pharmacology*; D018786:Bone Substitutes; D002130:Calcium Phosphates; D002460:Cell Line; D006031:Glycosylation; D008297:Male; D051379:Mice; D010012:Osteogenesis / Q000187:drug effects*; D019736:Prostheses and Implants; D051381:Rats; D017208:Rats, Wistar
chemical_list: C525720:Bmp2 protein, rat; D055396:Bone Morphogenetic Protein 2; D018786:Bone Substitutes; D002130:Calcium Phosphates; C020243:calcium phosphate; D000469:Alkaline Phosphatase