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

Paper ID Volume ID Publish Year Pages File Format Full-Text
9093 617 2010 7 PDF Available
Title
The effect of two point mutations in GDF-5 on ectopic bone formation in a β-tricalciumphosphate scaffold
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 < 0.0001) and 1.4-fold higher levels compared to BMP-2 (p < 0.006). Bone area in histology was significantly higher in mutant GDF-5 versus all other groups at 4 weeks; however, at 8 weeks BMP-2 reached a similar neo-bone formation like mutant GDF-5. Micro-CT evaluation confirmed higher values in the mutant GDF-5 and BMP-2 groups compared to wild type GDF-5. In conclusion, the mutant GDF-5 showed superior bone formation capacity than GDF-5, and a faster induction at similar final outcome as BMP-2. Mutant GDF-5 thus represents a promising new GDF-5 variant for bone regeneration possibly acting via an increased binding affinity to the BMP-type I receptor.

Keywords
Growth factor; Mutation; GDF-5; Heterotopic bone formation; Osteogenic differentiation; Beta tricalcium phosphate ceramic
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The effect of two point mutations in GDF-5 on ectopic bone formation in a β-tricalciumphosphate scaffold
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Publisher
Database: Elsevier - ScienceDirect
Journal: Biomaterials - Volume 31, Issue 14, May 2010, Pages 3878–3884
Authors
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Subjects
Physical Sciences and Engineering Chemical Engineering Bioengineering
Get Full-Text Now
Don't Miss Today's Special Offer
Price was $35.95
You save - $31
Price after discount Only $4.95
100% Money Back Guarantee
Full-text PDF Download
Online Support
Any Questions? feel free to contact us