BONE CELL CALCIUM REGULATION

这项研究的长期目标是了解 骨细胞钙调节的作用。内生与外生 将评估控制此参数的因素，并 这些因素与人体内钙的潜在相互关系 将对骨代谢的调节进行评估。其影响 甲状旁腺激素(PTH)、前列腺素E2(PGE2)、表皮 将研究生长因子和白介素I(IL-L 正常大鼠成骨细胞和骨肉瘤细胞系UMR-106 和SAOS-2。推定的影响之间的相互关系 这些药物对钙和磷脂酰肌醇的代谢也有影响 通过研究这种磷脂在体内的调节作用来研究 通过研究肌醇磷酸盐对骨细胞的影响 在这些分离的细胞系统中的钙动员。 花生四烯酸钙与胞浆钙意愿的相互关系 也被评估和花生四烯酸的影响 细胞内钙动员也将被研究。角色 蛋白激酶C在成骨细胞钙调节中的作用 新陈代谢也将使用抑制剂和激活剂进行研究。 这种酶。蛋白质、DNA合成和纤溶酶原的研究 激活器也将进行尝试，以建立关联 胞浆内钙离子的变化。花生四烯酸代谢 还将在各种电池系统中进行研究，以更好地 了解环氧合酶产物之间的相互关系 和胞内钙。细胞内钙水平将被测量 用悬浮液中的细胞进行Fura-2荧光分析 贴在封面纸上。将研究磷酸肌醇的代谢 薄层层析和离子交换层析 高效液相色谱。花生四烯酸代谢 也将通过高效液相色谱进行研究。 这些研究应该有助于更好地理解自然界 骨细胞代谢的研究和对治疗的发展的帮助 全身性和局限性骨代谢紊乱。

The long term objective of this study is to understand the nature of bone cell calcium regulation. The endogenous and exogenous factors that control this parameter will be assessed and the potential interrelationships between these factors and calcium in the regulation of bone metabolism will be evaluated. The effects of parathyroid hormone (PTH), prostaglandin E2 (PGE2), epidermal growth factor (EGF) and interleukin -I(IL-l) will be studied in normal rat osteoblastic cells and the osteosarcoma lines - UMR-106 and SaOS-2. The interrelationships between putative effects of these agents on calcium and phosphoinositide metabolism will also be studied by investigating the regulation of this phospholipid in the bone cells and by studying the effects of inositol phosphates on calcium mobilization in these isolated cell systems. Interrelationships between arachidonic and cytosolic calcium will also be evaluated and the effects of arachidonic acid on intracellular calcium mobilization will also be studied. The role of protein kinase C in the regulation of osteoblastic calcium metabolism will also be studied using inhibitors and activators of this enzyme. Studies on protein, DNA synthesis and plasminogen activator will also be conducted in an attempt to make correlations with changes in cytosolic calcium. Arachidonic acid metabolism will also be studied in the various cell systems to better understand the interrelationship between cyclooxygenase products and cytosolic calcium. Cytosolic calcium levels will be measured using the Fura 2 fluorescent assay with cells in suspension and attached to coverslips. Phosphoinositol metabolism will be studied with thin layer and ion exchange chromatography and high performance liquid chromatography. Arachidonic acid metabolism will also be studied by high performance liquid chromatography. These studies should lead to a better understanding of the nature of bone cell metabolism and aid in the development of therapy for systemic and localized bone metabolic disorders.