Disulfide bridge conformers of mature BMP are inhibitors for heterotopic ossification

Heterotopic ossification is a frequent complication in patients who have su ffered head and neck traumas or undergone total hip replacement. Heterotopi c ossification occurs when osteogenic precursor cells present at the ectopi c site receive the necessary signal(s) to differentiate into osteoblasts. A t the protein level, the key factors in differentiation of cells to the ost eogenic lineage are BMPs. Stable BMP variants derived from the identical am ino acid sequence but with different disulfide bridge configurations have b een investigated and found to be capable of inhibiting ossification in vitr o and in vivo in rodents. These findings provide a concept for the straight forward development of a novel class of BMP antagonists that could lead to new treatments for traumatically and genetically induced heterotopic ossifi cation and also, possibly, for disorders in which other members of the TGF- beta superfamily are involved. (C) 2001 Academic Press.