The Use of Mass Spectrometry in Characterization of Bone Morphogenetic Proteins from Biological Samples

Abstract

1.1 Bone morphogenetic proteins Bone morphogenetic proteins (BMPs) are family of growth factors. (Chen et al., 2004; Vukicevic & Sampath, 2008) Discovered in context of bone biology, today they are recognized as important signaling molecules in wide range of biological processes, such as vertebrate embryonic development (Hogan, 1996), mesenchymal stem cell differentiation (Vukicevic & Grgurevic, 2009), kidney fibrosis, and more. For the last years BMP-2 and BMP-7 are used as therapeutics in orthopedics, harnessing their regenerative potential as growth factors. From the onset of medicine scholars have been aware of the bone regenerative potential. In 1965. Urist was first to show that demineralized bone matrix (DBM) can induce bone growth if implanted into extraskeletal site. Active component from DBM was named bone morphogenetic protein by Urist & Strates (1971). Purification, cloning and sequencing of BMP was done almost 20 years later by Wozney et al. (1988). They showed that BMP is not a single protein but a family of growth factors. From introduction of the BMP term through cloning and sequencing of individual BMPs in late 1980s, scientific output in the field has constantly grown and has exceeded 1500 papers in 2010. (Figure 1) BMPs are part of transforming growth factor (TGF) superfamily of proteins. In humans TGFsuperfamily constitutes of 37 proteins. (Figure 2) Beside BMPs, TGFsuperfamily includes TGFproteins, inhibins (INH), growth/differentiation factors (GDF) and few others: artemin (ARTN), glial cell line-derived neurotrophic factor (GDNF), left-right determination factor 1 (LFTY1), LFTY2, muellerian-inhibiting factor (MIS), nodal homolog (NODAL), neurturin (NRTN) and persephin (PSPN). BMPs are functionally and structurally very conserved throughout animal kingdom. Their biological importance is reflected through functional and structural redundancy of different BMPs in single species. BMPs are translated as pre-propeptides. Signal peptide targets them for secretion out of cell. Prodomain is two thirds to four fifths of total peptide length and The Use of Mass Spectrometry in Characterization of Bone Morphogenetic Proteins from Biological Samples