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Pro-forms of growth factors have received intensive scientific attention recently because in some cases different biological activities have been ascribed compared with the mature growth factors. Examples are the pro-apoptotic role of the nerve growth factor (NGF) proform (proNGF) or the latency of the transforming growth factor (TGF)-␤ pro-form (proTGF-␤). To investigate a possible biological function of the pro-form of bone morphogenetic protein (BMP)-2, a member of the TGF-␤ family, mature BMP-2, proBMP-2, and the isolated pro-peptide were recombinantly produced in Escherichia coli cells, and a biophysical comparison was performed. Protocols were developed that allowed efficient refolding and subsequent purification of the proteins. ProBMP-2 could be processed to an N-terminally truncated form of BMP-2, digit removed BMP-2 (drBMP-2), that possessed biological activity, i.e. it induced ectopic bone formation. Bone inducing activity was also displayed by proBMP-2. The three proteins were characterized both by fluorescence and CD spectroscopy. From these analyses, predominant ␤-sheet secondary structural elements in the pro-peptide were deduced. The thermodynamic stability of the pro-peptide was determined by chemical unfolding assays. As in the case of NGF/proNGF, the mature part of BMP-2 stabilized the structure of the pro-peptide moiety. However, in contrast to NGF/proNGF, the pro-peptide did not stimulate oxidative folding of the mature part in vitro.

At the time we prefer OCT instead of ACT given the correct indication.

The osteogenic potential of bone and bone matrix has been characterised only by its biological effects and the parameters influencing it. Recently, the osteoinductive ability of bone matrix had been defined chemically by the description of a bone morphogenetic protein (BMP), and the parameters of osteogenic factors from different species have now been recognised. The current state of isolation, purification and characterisation of these factors is summarised in this review. General aspects of the isolation and testing of BMP preparations, and the results of orthotopic application of BMP implants, including clinical cases, are reported.

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