Disulfide bridge conformers of mature BMP are inhibitors for heterotopic ossification.
Heterotopic ossification is a frequent complication in patients who have suffered head and neck traumas or undergone total hip replacement. Heterotopic ossification occurs when osteogenic precursor cells present at the ectopic site receive the necessary signal(s) to differentiate into osteoblasts. At the protein level, the key factors in differentiation of cells to the osteogenic lineage are BMPs. Stable BMP variants derived from the identical amino acid sequence but with different disulfide bridge configurations have been investigated and found to be capable of inhibiting ossification in vitro and in vivo in rodents. These findings provide a concept for the straightforward development of a novel class of BMP antagonists that could lead to new treatments for traumatically and genetically induced heterotopic ossification and also, possibly, for disorders in which other members of the TGF-beta superfamily are involved.
Weber
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Klinik für Gesichts- und Kieferchirurgie, Institut für Klinische Chemie, Universitätsspital Zürich, Rämistrasse 100, Zürich, 8091, Switzerland. weber@zzmk.unizh.ch
Eyrich
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G
Grätz
K W
KW
Thomas
R M
RM
Maly
F E
FE
Sailer
H F
HF
D000818:Animals; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins / Q000037:antagonists & inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D002113:Calcification, Physiologic; D002460:Cell Line; D019281:Dimerization; D004220:Disulfides / Q000737:chemistry; D051379:Mice; D009999:Ossification, Heterotopic / Q000473:pathology / Q000517:prevention & control*; D017510:Protein Folding; D051381:Rats; D016212:Transforming Growth Factor beta
C525719:Bmp2 protein, mouse; C525720:Bmp2 protein, rat; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins; D004220:Disulfides; D016212:Transforming Growth Factor beta