Non-glycosylated BMP-2 can induce ectopic bone formation at lower concentrations compared to glycosylated BMP-2

• Published in: Journal of controlled release 2012-04, Vol.159 (1), p.69-77
• Main Authors: van de Watering, F.C.J., van den Beucken, J.J.J.P., van der Woning, S.P., Briest, A., Eek, A., Qureshi, H., Winnubst, L., Boerman, O.C., Jansen, J.A.
• Format: Article
• Language: English
• Subjects: Alkaline Phosphatase - metabolism; Animals; bioactive properties; Biological and medical sciences; Bone biomaterials; bone formation; Bone growth; Bone implants; Bone Marrow Cells - cytology; Bone Marrow Cells - drug effects; Bone morphogenetic protein 2; Bone Morphogenetic Protein 2 - pharmacology; Bone substitute material; Bone Substitutes; Calcium phosphate; Calcium Phosphates; Cell Line; Controlled release; General pharmacology; Glycosylation; Growth factor release; Growth factors; Guanine nucleotide-binding protein; In vivo response; Male; Mammalian cells; Medical sciences; Mice; Ossification (ectopic); Osteogenesis; Osteogenesis - drug effects; Pharmaceutical technology. Pharmaceutical industry; Pharmacology. Drug treatments; Prostheses and Implants; proteins; Rats; Rats, Wistar; rhBMP-2
• ISSN: 0168-3659; 1873-4995
• DOI: 10.1016/j.jconrel.2011.12.041

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 (2–20μg/implant) on the CaP-based bone substitute material and implanted for 4 and 12weeks. 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. Calcium phosphate based bone substitute material was loaded with non-glycosylated or glycosylated BMP-2. Despite lower release in vitro, ngBMP-2 significantly increased ectopic bone formation compared to gBMP-2. [Display omitted]