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

前列腺源性骨生长因子的纯化及其在骨质疏松治疗中的应用

• 批准号: 02557111
• 负责人: MATSUMOTO Toshio
• 金额: $ 7.23万
• 依托单位: Uaniversity of Tokyo
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Developmental Scientific Research (B)
• 财政年份: 1990
• 资助国家: 日本
• 起止时间: 1990 至 1992
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-02557111/
• 关键词: prostate; bone formation; grow factor; osteoporosis; 骨形成因子

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

前列腺中含有大量的各种生长因子，前列腺癌骨转移引起明显的成骨改变。为探索骨质疏松症治疗的新途径，本研究从手术或经尿道切除的肥大前列腺组织的尿素提取物中，筛选出一种能引起骨质疏松症成骨改变的因子，并探讨其在骨质疏松症骨形成中的应用。并且在具有进展活性的级分中发现强的成骨活性。因此，通过使用阴离子交换柱、反相柱、凝胶过滤柱、阳离子交换柱、反相柱、凝胶过滤肝素亲和柱、阴离子交换柱和反相柱的顺序高效液相色谱法纯化进展活性。虽然进展活性不能纯化到单一条带 ...更多信息 在SDS-PAGE上，进展活性的最终级分在成骨样细胞中具有强的促有丝分裂活性。然而，该馏分并没有刺激碱性磷酸酶活性在这些成骨细胞，也没有增强异位骨形成在体内植入胶原颗粒到皮下组织中的大鼠。为了鉴定该因子，酶切后进行肽图分析，并测定酶切片段的氨基酸序列。虽然获得了与高迁移率族蛋白-1、富含半胱氨酸蛋白、组蛋白H1B和H1 O等核蛋白同源的氨基酸序列，但没有一个片段与已知的生长因子具有同源性，并且有一些片段的氨基酸序列未知。由于我们有人前列腺cDNA文库，这些未知肽的cDNA克隆可能揭示一种新的前列腺源性成骨因子。少

项目成果

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