BONE CELLS AND THE METABOLISM OF VITAMIN D3

骨细胞和维生素 D3 的代谢

基本信息

批准号：
3071159
负责人：
J. Edward PUZAS
金额：
$ 4.06万
依托单位：
UNIVERSITY OF ROCHESTER
依托单位国家：
美国
项目类别：
财政年份：
1983
资助国家：
美国
起止时间：
1983-12-01 至 1988-11-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/3071159
关键词：
1,25 dihydroxycholecalciferol 25 hydroxycholecalciferol aging calcium metabolism gel filtration chromatography high performance liquid chromatography hydrolase nutrition related tag orphan disease /drug osteocytes osteogenesis imperfecta tissue /cell culture vitamin metabolism

项目摘要

Studies on the in vitro metabolism of 25-hydroxyvitamin D3 (25(OH)D3) by both renal and extrarenal cells has extended our knowledge of the vitamin D3 endocrine system. For the most part these types of experiments have utilized isolated cells in either monolayer culture or in suspension. At present, a number of cell types have been assayed for 25-hydroxyvitamin-D3-1- and 24-hydroxylase (1-hydroxylase and 24-hydroxylase) activity. Cells isolated from kidney, bone, intestine, placenta, decidua and chorioallantoic membrane appear to be able to produce both 1,25(OH)2D3 and 24,25-dihydroxyvitamin-D3 (24,25(OH)2D3) from 25-hydroxyvitamin D3 (25(OH)D3) and cells isolated from liver, skin, skeletal muscle, heart muscle, cartilage, etc. have no such activity (except for the possible synthesis of 24,25(OH)2D3 by cartilage). These observations have led to the proposition of a new hypothesis which states that all tissues involved in homeostasis of calcium and phosphorous can synthesize at least small amounts of 1,25(OH)2D3, probably for local use. In general it is the aim of this proposal to further test this hypotesis by characterizing the ability of extrarenal cells, especially bone cells, to synthesize 1,25(OH)2D3 and 24,25(OH)2D3. Specifically, experiments will be performed to determine 1) the effect of agents known to mediate mineral homeostasis on bone cell 1- and 24- hydroxylase activities, 2) the effect of age and state of differentiation of bone cells on 1- and 24-hydroxylase activities, 3) the biological effectiveness of the 1,25(OH)2D3 synthesized b bone cells, and 4) other cell types which can synthesize 1,25(OH)2D3 and 24,25(OH)2D3 and may conform to the above stated hypothesis. The methodology will include all of the techniques for the isolation and culture of bone and other cell types as well as those for the separation, identification and metabolism of vitamin D3 metabolites. If these goals can be achieved the ensuing data should support the physiological importance of extrarenal 1,25(OH)2D3 synthesis and may change the way we view the integrated control of mineral metabolism.

研究25-羟基维生素D3（25（OH）D3）的体外代谢的研究肾脏和外部细胞都扩展了我们对维生素的了解 D3内分泌系统。在大多数情况下，这些类型的实验具有在单层培养物或悬浮液中利用分离的细胞。在目前，已经分析了许多细胞类型 25-羟基维生素-D3-1-和24-羟化酶（1-羟化酶和 24-羟化酶）活性。从肾脏，骨骼，肠子中分离出的细胞，胎盘，Decidua和绒毛膜膜似乎能够产生来自1,25（OH）2d3和24,25-二羟基维生素D3（24,25（OH）2d3） 25-羟基维生素D3（25（OH）D3）和从肝脏，皮肤分离的细胞骨骼肌，心肌，软骨等没有这样的活动（除了通过软骨合成24,25（OH）2d3）。这些观察结果导致了一个新假设的主张，该假设指出所有参与钙和磷稳态的组织都可以合成至少少量的1,25（OH）2d3，可能用于本地使用。通常，该提议的目的是进一步测试这种低血通过表征外部细胞，尤其是骨细胞的能力，合成1,25（OH）2d3和24,25（OH）2d3。具体而言，实验将进行确定1）已知介导矿物的剂的作用骨细胞1-和24-羟化酶活性的稳态，2）效果 1-羟化酶和24-羟化酶上骨细胞分化的年龄和状态活动，3）1,25（OH）2d3合成B的生物学有效性B 骨细胞和4）其他可以合成1,25（OH）2d3和的细胞类型 24,25（OH）2d3，可能符合上述假设。该方法将包括隔离的所有技术，骨骼和其他细胞类型的培养以及分离的培养维生素D3代谢产物的鉴定和代谢。如果可以实现这些目标，则随后的数据应支持外肾外1,25（OH）2d3合成的生理重要性，可能会改变我们观察矿物质代谢的综合控制的方式。