REGULATION OF OSTEOCALCIN CONCENTRATIONS IN BLOOD

血液中骨钙素浓度的调节

• 批准号: 3071363
• 负责人: Caren Gundberg
• 金额: $ 6.88万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1987
• 资助国家: 美国
• 起止时间: 1987-09-30 至 1992-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3071363
• 关键词: blood proteins; bone metabolism disorder; calcium binding protein; drug administration rate /duration; hormone regulation /control mechanism; hydroxyapatites; laboratory rat; monoclonal antibody; osteocalcin; parathyroidectomy; physiologic bone resorption; radioimmunoassay; radiotracer

Osteocalcin is an abundant calcium binding protein indigenous to the organic matrix of bone. Development of radioimmunoassays for osteocalcin revealed that it circulates in blood. Several studies have suggested that the measurement of serum osteocalcin may be of use in the evaluation and treatment of patients with metabolic bone disease. Serum osteocalcin is generally regarded as a marker of bone formation, but multiple factors may determine osteocalcin concentrations in blood. These include: bone cell synthesis and catabolism of the protein, regulation of osteocalcin affinity for hydroxyapatite, and clearance of the protein or its metabolic fragments by the kidney. Long term objectives are to a) provide a clear understanding of the factors which regulate osteocalcin concentration in blood, b) establish the function of the protein in bone, and c) develop precise biochemical assays for use in the diagnosis and treatment of metabolic bone disorders. The specific aims of this proposal are to: 1. investigate the qualitative and quantitative effects of chronic and acute administration of calcitropic hormones and minerals on circulating osteocalcin in normal and thyroparathyroidectomized rats. 2. determine if there are any acute changes in the binding affinity of osteocalcin to hydroxyapatite produced by alterations in local mineral concentrations. 3. study the relationship of serum osteocalcin to calcium flux in 45Ca prelabelled rats. 4. determine if there are alterations in the calcemic or phosphatemic response to calcitropic hormones in osteocalcin deficient rats. 5. study the regulation of the renal handling of osteocalcin in isolated perfused rat kidney. 6. examine the regulation of the catabolism of osteocalcin in perfused isolated rat hindquarters. 7. identify specific fragments of osteocalcin produced during bone resorption. 8. produce monoclonal antibodies to such fragments for use in clinical studies. 9. establish normal values of osteocalcin in human studies 10. evaluate relationships between osteocalcin and other biochemical and histological parameters of bone metabolism in normal individuals and those with metabolic bone disease.

骨钙素是一种丰富的钙结合蛋白与土著与 骨骼的有机基质。 放射免疫测定的开发 对于骨钙素，它表明它在血液中循环。 一些 研究表明血清的测量 骨钙素可能用于评估和治疗 代谢骨病的患者。 血清骨钙素是 通常被视为骨形成的标记，但多个 因素可能决定血液中的骨钙素浓度。 这些 包括：蛋白质的骨细胞合成和分解代谢， 对羟基磷灰石的骨钙素亲和力的调节，以及 肾脏清除蛋白质或其代谢片段。 长期目标是a）对 调节血液中骨钙素浓度的因素，b） 建立蛋白质在骨骼中的功能，c）发展 精确的生化测定用于诊断和治疗 代谢骨障碍。 该提案的具体目的是： 1。研究慢性的定性和定量效应 以及在 正常和甲状腺脊髓钙化的骨钙素循环 老鼠。 2。确定结合是否有任何急性变化 骨钙素与羟基磷灰石的亲和力是由改变产生的 在局部矿物质浓度中。 3。研究血清骨钙素与钙通量的关系 45CA预先标记的大鼠。 4。确定钙化或 对骨钙素的钙氨基激素的磷酸症反应 不足的大鼠。 5。研究骨钙素肾脏处理的调节 孤立的灌注大鼠肾脏。 6。检查骨钙素分解代谢的调节 灌注孤立的大鼠后肢。 7。确定在 骨吸收。 8。生产此类片段的单克隆抗体用于 临床研究。 9。在人类研究中建立骨钙素的正常值 10。评估骨钙素和其他的关系 骨代谢的生化和组织学参数 正常人和患有代谢骨病的人。