REGULATION OF OSTEOCALCIN CONCENTRATIONS IN BLOOD

骨钙素是一种丰富的钙结合蛋白，天然存在于 骨骼的有机基质。放射免疫分析方法的研究进展 因为骨钙素揭示了它在血液中循环。几个 研究表明，血清的测量 骨钙素可用于评估和治疗骨质疏松症 代谢性骨病患者。血清骨钙素是 通常被认为是骨形成的标志，但有多个 各种因素可能决定血液中骨钙素的浓度。这些 包括：骨细胞蛋白质的合成和分解代谢， 骨钙素对羟基磷灰石亲和力的调节 肾脏清除蛋白质或其代谢碎片。 长期目标是a)提供对 调节血液中骨钙素浓度的因素，b) 确定蛋白质在骨骼中的功能，以及c)发展 用于诊断和治疗的精密生化分析 代谢性骨骼疾病。 这项建议的具体目的是： 1.调查慢性疾病的定性和定量影响 急性应用促降钙素和矿物质治疗 正常和甲状旁腺切除术后循环骨钙素的变化 老鼠。 2.确定绑定中是否有任何急性更改 骨钙素对蚀变产生的羟基磷灰石的亲和力 在当地矿物质浓度中。 3.研究大鼠血清骨钙素与钙流的关系。 45Ca预先标记的大鼠。 4.确定血钙是否有变化或 骨钙素对促钙激素的磷酸化反应 有缺陷的老鼠。 5.研究骨钙素在肾脏中的转运规律。 分离的灌流大鼠肾脏。 6.检测骨钙素分解代谢的调节。 灌流隔离的大鼠后肢。 7.确定骨钙素产生的特定片段 骨吸收。 8.生产针对这些片段的单抗，用于 临床研究。 9.建立人体研究中骨钙素的正常值 10.评估骨钙素与其他 大鼠骨代谢生化和组织学参数 正常人和代谢性骨病患者。

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.