The effect of two point mutations in GDF-5 on ectopic bone formation in a β-tricalciumphosphate scaffold
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...
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| Main Authors: | , , , , , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
18 February 2010
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| In: |
Biomaterials
Year: 2010, Volume: 31, Issue: 14, Pages: 3878-3884 |
| ISSN: | 1878-5905 |
| DOI: | 10.1016/j.biomaterials.2010.01.109 |
| Online Access: | Resolving-System, lizenzpflichtig, Volltext: https://doi.org/10.1016/j.biomaterials.2010.01.109 Verlag, lizenzpflichtig, Volltext: https://www.sciencedirect.com/science/article/pii/S0142961210001419 
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| Author Notes: | Philip Kasten, Ingo Beyen, Dirk Bormann, Reto Luginbühl, Frank Plöger, Wiltrud Richter |
| Summary: | 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. |
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| Item Description: | Gesehen am 07.03.2023 |
| Physical Description: | Online Resource |
| ISSN: | 1878-5905 |
| DOI: | 10.1016/j.biomaterials.2010.01.109 |