Characterisation of secreted phosphoprotein 24

Secreted phosphoprotein 24 (spp24) is a novel 24-kDa non-collagenous protein that was originally isolated from the acid demineralised extract of bovine cortical bone (Hu et al. 1995). The presence of spp24 in bone immediately suggested a potential role for the protein in the processes that occurred there. The N-terminal segment of the protein is related in sequence to the cystatin family of thiol protease inhibitors. It was therefore suggested that spp24 might inhibit thiol protease activity during bone turnover (Hu et al. 1995).;Three million people in the UK suffer from osteoporosis (National Osteoporosis Society estimated figure) and their care and treatment costs the NHS and the taxpayer £942 million every year (Dolan and Torgerson 1998). Therefore, it is essential that we begin to understand the genetic basis and the factors that can predispose people, to osteoporosis and many other bone diseases. If spp24 has a functional role in the process of bone remodelling it is likely that it may influence the development or severity of osteoporosis.;This study determines the human SPP2 gene, encoding the spp24 protein, to comprise 8 exons with apparently TATA-less promoter. The gene is shown to have multiple transcription initiation sites, which demonstrate some tissue specificity. An extensive expression study was carried out on the human and mouse gene encoding spp24, indicating that the gene has an expression pattern of a tissue-specific nature, being expressed predominantly in liver.;Theoretical studies and computational methods were used to analyse spp24 from several species and proteins showing homology to spp24. These studies gave a good indication of the areas of the protein and specific residues that are likely to be critical to the function of spp24. The results supported the speculation that spp24 does not act as a typical cystatin, but instead is likely to have a fetuin-like function or an antimicrobial function..