REGULATION OF OSTEOCALCIN CONCENTRATIONS IN BLOOD

骨钙素是一种丰富的钙结合蛋白， 骨骼的有机基质 放射免疫分析的发展 骨钙素在血液中循环。 几 研究表明， 骨钙素可用于评估和治疗 代谢性骨病患者。 血清骨钙素 通常被认为是骨形成的标志物，但多种 这些因素可以决定血液中骨钙素的浓度。 这些 包括：蛋白质的骨细胞合成和分解， 调节骨钙素对羟基磷灰石的亲和力，和 肾脏对蛋白质或其代谢片段的清除。 长期目标是：（a）明确了解 调节血液中骨钙素浓度的因子，B） 建立蛋白质在骨中的功能，以及c）开发 用于诊断和治疗的精确生化测定 代谢性骨骼疾病 这项建议的具体目标是： 1. 调查慢性病的定性和定量影响 以及促钙激素和矿物质的急性给药， 正常人和甲状腺甲状旁腺切除后的循环骨钙素 大鼠 2. 确定约束力是否有任何急剧变化 骨钙素对由改变产生的羟基磷灰石的亲和力 在当地的矿物质浓度。 3. 探讨血清骨钙素与钙流的关系 ~（45）Ca预标记大鼠。 4. 确定是否有改变在calculator或 骨钙素对促钙激素的血磷反应 缺乏的老鼠 5. 研究肾对骨钙素的调控作用， 离体灌流大鼠肾。 6. 研究骨钙素的代谢调节， 灌注的离体大鼠后躯。 7. 识别过程中产生的骨钙素的特定片段 骨吸收 8. 产生针对这些片段的单克隆抗体，用于 临床研究。 9. 骨钙素人体研究正常值的建立 10. 评价骨钙素与其他 骨代谢的生化和组织学参数， 正常个体和患有代谢性骨病的个体。

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.