The effect of two point mutations in GDF-5 on ectopic bone formation in a β-tricalciumphosphate scaffold

• Published in: Biomaterials 2010-05, Vol.31 (14), p.3878-3884
• Main Authors: Kasten, Philip, Beyen, Ingo, Bormann, Dirk, Luginbühl, Reto, Plöger, Frank, Richter, Wiltrud
• Format: Article
• Language: English
• Subjects: Advanced Basic Science; Alkaline Phosphatase - metabolism; Animals; Beta tricalcium phosphate ceramic; Bone and Bones - diagnostic imaging; Bone and Bones - drug effects; Bone and Bones - enzymology; Bone and Bones - pathology; Calcium Phosphates - chemistry; Choristoma - pathology; Dentistry; Enzyme Activation - drug effects; GDF-5; Growth Differentiation Factor 5 - chemistry; Growth Differentiation Factor 5 - genetics; Growth Differentiation Factor 5 - metabolism; Growth Differentiation Factor 5 - pharmacology; Growth factor; Heterotopic bone formation; Humans; Mice; Mice, SCID; Mutation; Osteogenesis - drug effects; Osteogenic differentiation; Point Mutation - genetics; Protein Structure, Secondary; Recombinant Proteins - chemistry; Recombinant Proteins - genetics; Recombinant Proteins - metabolism; Recombinant Proteins - pharmacology; Tissue Scaffolds - chemistry; X-Ray Microtomography
• ISSN: 0142-9612; 1878-5905
• DOI: 10.1016/j.biomaterials.2010.01.109

Abstract The osteoinductivity of human growth-and-differentiation factor-5 (GDF-5) is well established, but a reduced amount of ectopic bone is formed compared to other members of the bone morphogenetic protein (BMP) family like BMP-2. We hypothesized that swap of two BMP-receptor-interacting residues of GDF-5 to amino acids present in BMP-2 (methionine to valine at the sites 453 and 456) may improve the bone formation capacity of the mutant GDF-5. Heterotopic bone formation of a mutant GDF-5 coated β-TCP carrier was compared to carriers coated with similar amounts (10 μg) of GDF-5 and BMP-2 in SCID mice. Four week explants revealed 6-fold higher ALP activity in the mutant GDF-5 versus the wild type GDF-5 group ( p