ROLE OF MEMBRANES AND MINERALIZATION OF BONES AND TEETH

膜的作用以及骨骼和牙齿的矿化

• 批准号: 6362921
• 负责人: Barbara D. Boyan
• 金额: $ 22.42万
• 依托单位: UNIVERSITY OF TEXAS HLTH SCIENCE CENTER
• 依托单位国家: 美国
• 财政年份: 1981
• 资助国家: 美国
• 起止时间: 1981-03-01 至 2003-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6362921
• 关键词: 1,25 dihydroxycholecalciferol; 25 hydroxycholecalciferol; SDS polyacrylamide gel electrophoresis; acylation; alkaline phosphatase; autocrine; biological models; biological signal transduction; bone development; bone metabolism; calcification; calcium flux; cartilage development; cartilage metabolism; cell membrane; cholecalciferol; chondrocytes; dental development; dexamethasone; extracellular matrix; high performance liquid chromatography; hydrolysis; hydroxyapatites; inositol phosphates; laboratory rabbit; laboratory rat; lipid metabolism; normal ossification; nutrition related tag; phosphatidylinositols; phospholipase A2; phospholipase C; phospholipase D; phospholipids; prostaglandin E; proteolipids; tissue /cell culture; transforming growth factors; vitamin D; vitamin metabolism

DESCRIPTION: (Adapted from investigator's Abstract) This proposal uses a cartilage cell model to address how calcifying cells modulate events at distal sites in the extracellular matrix and in particular, on the role of matrix vesicles (MV) in this process. It is based on the hypothesis that vitamin D metabolites regulate MV composition via genomic mechanisms through the classic vitamin D receptor (VDR) and membrane-mediated pathways. In addition, chondrocytes synthesize and secrete vitamin D metabolites, as well as other autocoids like prostaglandin E2, which, in turn, interact directly with the MV membrane to nongenomically regulate MV activity. Three specific aims are proposed. The first is to examine the biochemical mechanisms involved in the production of vitamin D metabolites by chondrocyte cultures. Regulation of l,25-(OH)2 D3 (1,25) and 24,25-(OH)2 D3 (24,25) production by 1,25 and 24,25 will be examined. Changes in 1-alpha- and 24-hydroxylases, as well as gene expression of the 24-hydroxylase, will be examined as a function of hormone dose and time. The role of the VDR or membrane-initiated events will be assessed using structural analogs of 1,25 and 24,25. The second is to examine the regulation of membrane signaling systems by Vitamin D metabolites. The mechanisms for differential regulation of protein kinase C (PKC) by 1,25 and 24,25 in plasma membranes (PM) and MV and use analogues of 1,25 and 24,25 to assess the relative contributions of the VDR, as well as the role of functional moieties of the vitamin D metabolites in their nongenomic action on MV membranes will be examined. The interrelationship between the PKC and PGE2 pathways will also be determined. The third is to to characterize the membrane effects of 1,25 and 24,25 on the functional properties of MV's. The regulation of stromelysin-1 by 1,25 and 24,25 will be examined, and will focus on the role of cell maturation state and the relative contributions of the VDR and membrane-mediated pathways in regulating stromelysin-1 synthesis, secretion, and activation. Nongenomic regulation of MV's will be assessed in functional assays of calcification in proteoglycan-containing gelatin gels. This work will have major implications for our understanding of MV and how cells that calcify their matrix are able to regulate these extracellular organelles at distant sites.

描述：（根据调查员的摘要进行了改编）该建议使用 软骨细胞模型以解决钙化细胞如何调节事件 细胞外基质中的远端位点，尤其是在 在此过程中的基质囊泡（MV）。 它基于以下假设 维生素D代谢物通过基因组机制调节MV组成 经典的维生素D受体（VDR）和膜介导的途径。 在 加上软骨细胞合成并分泌维生素D代谢物 就像其他类型类似于Prostaglandin E2一样，它又直接相互作用 与MV膜一起进行非原始调节MV活性。 三个具体 提出了目标。 首先是检查生化机制 参与软骨细胞培养物生产维生素D代谢产物。 L，25-（OH）2 D3（1,25）和24,25-（OH）2 D3（24,25）的法规生产 将检查1,25和24,25。 1-α-和24-羟化酶的变化， 以及24-羟化酶的基因表达，将被检查为 激素剂量和时间的功能。 VDR或 将使用1,25的结构类似物评估膜引起的事件 和24,25。 第二个是检查膜信号的调节 维生素D代谢物的系统。 差分机制 在质膜中调节蛋白激酶C（PKC）1,25和24,25 （PM）和MV，并使用1,25和24,25的类似物评估相对 VDR的贡献以及功能部分的作用 维生素D代谢物在其对MV膜的非原位作用中将是 检查。 PKC和PGE2途径之间的相互关系也将 可以确定。 第三是表征1,25的膜效应 和MV的功能特性为24,25。 调节 将检查Stromelysin-1 x 1,25和24,25，并将重点放在角色上 细胞成熟状态和VDR的相对贡献 膜介导的途径在调节Stromelysin-1合成，分泌，分泌， 和激活。 MV的非原位调节将在评估中 含蛋白聚糖的明胶凝胶中钙化的功能测定。 这项工作将对我们对MV的理解以及如何理解产生重大影响 钙化基质的细胞能够调节这些细胞外 远处的细胞器。

项目成果

Direct effects of 1,25-dihydroxyvitamin D3 and 24,25-dihydroxyvitamin D3 on growth zone and resting zone chondrocyte membrane alkaline phosphatase and phospholipase-A2 specific activities.

1,25-二羟基维生素 D3 和 24,25-二羟基维生素 D3 对生长区和静止区软骨细胞膜碱性磷酸酶和磷脂酶 A2 比活性的直接影响。

• DOI: 10.1210/endo-123-6-2878
• 发表时间: 1988
• 期刊: Endocrinology
• 影响因子: 4.8
• 作者: Schwartz,Z;Schlader,DL;Swain,LD;Boyan,BD
• 通讯作者: Boyan,BD

Localization of 1,25-(OH)2D3-responsive alkaline phosphatase in osteoblast-like cells (ROS 17/2.8, MG 63, and MC 3T3) and growth cartilage cells in culture.

1,25-(OH)2D3 反应性碱性磷酸酶在成骨细胞样细胞（ROS 17/2.8、MG 63 和 MC 3T3）和培养的生长软骨细胞中的定位。

• 发表时间: 1989
• 期刊: The Journal of biological chemistry
• 作者: Boyan,BD;Schwartz,Z;Bonewald,LF;Swain,LD
• 通讯作者: Swain,LD

Comments on the clinical application of fibronectin in dentistry.

纤连蛋白在牙科中的临床应用评述。

• DOI: 10.1177/00220345880670021701
• 发表时间: 1988
• 期刊: Journal of dental research
• 影响因子: 7.6
• 作者: Pearson,BS;Klebe,RJ;Boyan,BD;Moskowicz,D
• 通讯作者: Moskowicz,D

Prostaglandins mediate the effects of 1,25-(OH)2D3 and 24,25-(OH)2D3 on growth plate chondrocytes in a metabolite-specific and cell maturation-dependent manner.

前列腺素以代谢物特异性和细胞成熟依赖性方式介导 1,25-(OH)2D3 和 24,25-(OH)2D3 对生长板软骨细胞的影响。

• DOI: 10.1016/s8756-3282(99)00014-9
• 发表时间: 1999
• 期刊: Bone
• 影响因子: 4.1
• 作者: Schwartz,Z;Gilley,RM;Sylvia,VL;Dean,DD;Boyan,BD
• 通讯作者: Boyan,BD

Ion-translocating properties of calcifiable proteolipids.

可钙化蛋白脂质的离子易位特性。

• DOI: 10.1177/00220345880670030101
• 发表时间: 1988
• 期刊: Journal of dental research
• 影响因子: 7.6
• 作者: Swain,LD;Boyan,BD
• 通讯作者: Boyan,BD