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The effect of two point mutations in GDF-5 on ectopic bone formation in a b-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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Published in: | Biomaterials 2010-05, Vol.31 (14), p.3878-3884 |
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creator | Kasten, Philip Beyen, Ingo Bormann, Dirk Luginbuehl, Reto Ploeger, Frank Richter, Wiltrud |
description | 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 b-TCP carrier was compared to carriers coated with similar amounts (10aaI14g) 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 (paa |
doi_str_mv | 10.1016/j.biomaterials.2010.01.109 |
format | article |
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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 b-TCP carrier was compared to carriers coated with similar amounts (10aaI14g) 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 (paa<aa0.0001) and 1.4-fold higher levels compared to BMP-2 (paa<aa0.006). Bone area in histology was significantly higher in mutant GDF-5 versus all other groups at 4 weeks; however, at 8aaweeks 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.</description><identifier>ISSN: 0142-9612</identifier><identifier>DOI: 10.1016/j.biomaterials.2010.01.109</identifier><language>eng</language><ispartof>Biomaterials, 2010-05, Vol.31 (14), p.3878-3884</ispartof><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids></links><search><creatorcontrib>Kasten, Philip</creatorcontrib><creatorcontrib>Beyen, Ingo</creatorcontrib><creatorcontrib>Bormann, Dirk</creatorcontrib><creatorcontrib>Luginbuehl, Reto</creatorcontrib><creatorcontrib>Ploeger, Frank</creatorcontrib><creatorcontrib>Richter, Wiltrud</creatorcontrib><title>The effect of two point mutations in GDF-5 on ectopic bone formation in a b-tricalciumphosphate scaffold</title><title>Biomaterials</title><description>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. 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title | The effect of two point mutations in GDF-5 on ectopic bone formation in a b-tricalciumphosphate scaffold |
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