Purification of prostate-derived bone growth factor and its application to the treatment of osteoporosis

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Prostate contains a large amount of various growth factors, and bone metastasis of prostate cancer causes marked osteogenic changes. In an effort to develop a new therapeutic approach to osteoporosis, the present study was undertaken to identify a factor (s) that causes the osteogenic changes and to seek for the application of such a factor to the stimulation of bone formation in patients with osteoporosis.Urea extract of hypertrophic prostatic tissues obtained at operation or transurethral resection contained both competence and progression growth factor activities, and a strong osteogenic activity was found in the fraction with progression activity. Therefore, the progression activity was purified by a sequencial high performance liquid chromatography using anion exchange, reversed phase, gel filtration, cation exchange, reversed phase, gel filtration heparin affinity, anion excahange and reversed phase columns. Although the progression activity could not be purified to a single band … More on SDS-PAGE, the final fraction of the progression activity had a strong mitogenic activity in osteoblast-like cells. However, the fraction did not stimulate alkaline phosphatase activity in these osteoblastic cells, nor did it enhance ectopic bone formation in vivo when implanted with collagen pellets into subcutaneous tissues in rats. Further analyzes of the osteogenic activity of this factor is neede.In an effort to identify this factor, peptide mapping was performed after enzymatic digestion of the fraction, and amino acid sequences of digested fragments were determined. Although homologous amino acid sequences with several nuclear proteins such as high mobility group protein-1, cysteine rich protein, histone H1B and H1O were obtained, none of the fagments exhibited homology with any known growth factors, and there were some fragments with unknown amino acid sequences. Because we have human prostatic cDNA library, cDNA cloning of these unknown peptide may reveal a novel prostate-derived osteogenic factor. Less