OSTEOCALCIN SYNTHESIS AND CATABOLISM IN VIVO AND IN VITR

骨钙素是一种小蛋白质，占非胶原蛋白的20% 在骨骼的细胞外基质中。 目前的研究表明， 衍生自较高分子量的前体，并且其合成和 处理由1，25（OH）2D3调节。 它可能在调节 羟基磷灰石晶体生长和向骨部位募集破骨细胞 再吸收 虽然对结构和性质的研究 骨钙素在过去的几年里取得了进展，许多问题 关于它的生物合成和催化作用。 为了回答 这些问题，我们打算： 1)确定骨钙素的特定前体，并研究 促钙激素对大鼠和人骨合成和加工的影响 细胞培养。 2)识别骨形成过程中产生的骨钙素的特定片段 使用灭活骨和人的器官培养系统的再吸收 外周单核细胞 虽然骨钙素主要存在于骨中，但在血清中也存在痕量， 放射免疫测定的水平与骨密度相关 阵 为了开发血清骨钙素作为诊断标志物 对于代谢性骨病，我们将： 1)根据年龄、性别、荷尔蒙状态、饮食和 活动 2)血清骨钙素与骨代谢相关指标的关系 骨代谢，包括矿物质水平、碱性磷酸酶、尿 羟脯氨酸、促钙激素和直接组织形态计量学 测量. 将在正常个体中评估这些参数， 那些有骨骼疾病的人。 在骨钙素的骨吸收过程中，骨钙素的片段可能被 分泌到血液循环中。 我们将生产单克隆抗体， 合成和天然存在的骨钙素片段，并在 上述临床研究。 通过这些研究，我们希望提高对 骨钙素生物合成、催化及其对钙离子的作用 体内平衡和骨代谢。 我们还希望建立 骨钙素及其片段的测量作为重要的鉴别 用于诊断骨疾病的参数。

Osteocalcin is a small protein comprising 20% of the noncollagenous protein in the extracellular matrix of bone. Current studies indicate that it is derived from higher molecular weight precursors and that its synthesis and processing is regulated by 1,25(OH)2D3. It may play a role in regulating hydroxylapatite crystal growth and recruiting osteoclasts to sites of bone resorption. Although investigations into the structure and properties of osteocalcin have progressed in the past several years, many questions remain regarding its biosynthesis and catabolism. In an effort to answer these questions we intend to: 1) Identify specific precursors of osteocalcin and study the effect of calcitropic hormones on synthesis and processing using rat and human bone cells in culture. 2) Identify specific fragments of osteocalcin that are produced during bone resorption using an organ culture system of devitalized bone and human peripheral monocytes. While osteocalcin is found predominantly in bone, traces occur in serum and levels determined by radioimmunoassay correlate with the rate of bone formation. In order to develop serum osteocalcin as a diagnostic marker for metabolic bone disease, we will: 1) Establish normal values based on age, sex, hormonal status, diet, and activity. 2) Study the relationship between serum osteocalcin and other indices of bone metabolism including mineral levels, alkaline phosphatase, urinary hydroxyproline, calcitropic hormones, and direct histomorphometric measurements. These parameters will be assessed in normal individuals and those with bone disorders. During osteoclastic bone resorption, fragments of osteocalcin may be secreted into the circulation. We will produce monoclonal antibodies to synthetic and naturally occurring fragments of osteocalcin and test them in the clinical studies outlined above. Through these studies, we hope to improve the understanding of the biosynthesis and catabolism of osteocalcin and its role in calcium homeostasis and bone metabolism. We also hope to establish the measurements of osteocalcin and its fragments as important discriminatory parameters for the diagnosis of bone disorders.