Molecular mechanism of osteocyte lacunar canalicular system on PTH and bone quality

骨细胞腔隙微管系统对PTH和骨质量影响的分子机制

基本信息

批准号：
18390487
负责人：
AMIZUKA Norio
金额：
$ 11.17万
依托单位：
Niigata University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2006
资助国家：
日本
起止时间：
2006 至 2007
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-18390487/
关键词：
anatomy cell biology animal model bone parathyroid hormone

项目摘要

The aim of this research project is to clarify 1) osteocytic function of mineral regulation in bone, 2) effects of osteocytelacunar canalicular system onto bone quality, and 3) PTH action on the transport of bone mineral. (1) We generated a transgenic mouse expressing osteocytes-specific diphtheria toxin (DT) receptor. Following a injection of DT, 70%-80% of the osteocytes were dead, resulting in loss of bone minerals, intracortical porosity and microfractures (bone mineral regulation). This transgenic mouse was also resistant to unloading-induced bone loss, suggesting the osteocytic mechanotransduction. Both of bone mineral regulation and mechanotransduction by osteocytes appears to affect bone quality. (2) Using Schoen's silver staining, we have examined the distribution of the osteocytic lacunar canalicular system (OLCS) in mouse bones. Trabecular bones with high bone turnover displayed osteocytic cytoplasmic processes without any perceptible alignment. Also, many plump osteocytes w … More ere embedded in the mineralized bone in a disorderly manner. However, well-remodeled bone (epiphyseal trabecules and cortical bone), showed osteocytes with their spindle shape, organized so as to parallel the longitudinal axis of trabecular bone. Given the data gathered, the OLCS appears to assume an organized, probably function-related spatial distribution as normal bone remodeling goes on. OLCS seems to be a cellular factor to affect bone quality. (3) Finally, we have examined whether osteocytic osteolysis would occur after PTH administration. When injecting PTH, the size of osteocytic lacunae enlarged and the expression of sclerostin was reduced in the wild-type mice, but no such changes in the c-fos-/- mice in which osetoclastogenesis is totally inhibited. C-fos-/- mice showed disrupted OCLS, while wild-type mice had well-organized, functional OLCS, as described above. Thus, PTH signaling appears to be transduced from PTH receptor-bearing osteoblasts into osteocytes by means of functional OLCS, resulting in osteocytic ostelysis. Less

该研究项目的目的是阐明骨骼调节的骨细胞功能，2）骨细胞核细胞系统对骨质质量的影响，以及3）PTH对骨矿物质运输的作用。（1）我们产生了表达骨细胞特异性白喉（DT）受体的转基因小鼠。注射DT后，70％-80％的骨细胞死亡，导致骨矿物质，心脏内孔隙度和微裂缝（骨矿物质调节）的损失。该转基因小鼠还对卸载引起的骨质损失有抵抗力，这表明骨细胞机械转导。骨细胞的骨矿物质调节和机械转导的机械转导似乎都会影响骨骼质量。（2）使用Schoen的银色染色，我们检查了小鼠骨骼中骨细胞lacunar管系统（OLCS）的分布。骨转换高的小梁骨骼显示出骨细胞的胞质过程，而没有任何可感知的比对。同样，许多丰满的骨细胞都以无序的方式嵌入矿物质的骨骼中。然而，显示的骨骼（epiphyseal小梁和皮质骨）及其纺锤形的骨细胞显示，以使小梁骨的纵向轴平行。鉴于收集的数据，随着正常骨重塑的进行，OLC似乎假定有组织的，可能与功能相关的空间分布。 OLCS（3）最后，我们检查了PTH给药后是否会发生骨细胞骨溶解。当注射PTH时，在野生型小鼠中降低了骨细胞lac的大小和硬化蛋白的表达，但是在C-FOS - / - 小鼠中没有这种变化的骨质质质发生完全抑制。如上所述，C-FOS - / - 小鼠显示出破坏的OCL，而野生型小鼠具有良好的功能性OLC。这是通过功能性OLC从PTH受体的成骨细胞转换为骨细胞的PTH信号传导，从而导致骨细胞骨。较少的