权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Development of medicine for osteoporosis --- The effect of a new chemically-synthesized substance, KCA-098, on the melabolism of the bone

骨质疏松症药物的开发——新型化学合成物质KCA-098对骨代谢的影响

基本信息

批准号：
07672385
负责人：
KAWASHIMA Kohtaro
金额：
$ 1.34万
依托单位：
Teikyo University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1995
资助国家：
日本
起止时间：
1995 至 1996
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-07672385/
关键词：
Medicine for osteoporosis KCA-098 Osteoblast Osteoclast Alkaline phosphatase Osteocalcin オステルカルシン TRAP(+)MNC

项目摘要

KCA-098 was reported to stimulate bone formation and inhibit bone resorption in the culture of chick embryonic and fetal rat bones, suggesting that KCA-098 is the potent substance to improve the bone deseases such as osteoporosis. In this work, we did tow types of experiments. We first designed to see the direct effect of KCA-098 on the oteoblast, a bone forming cell, and osteoclast, a bone resorbing cell, to investigate that action mechanism of KCA-098 on the bone tissues in more detail. Next, we administered KCA-098 into the experimentally-induced osteoporotic rats to determine if KCA-098 is therapeutically applicable for the treatment of osteoporosis.In the culture of osteoblastic ROS 17/2.8 cells, KCA-098 increased alkaline phosphatase activity and the synthesis of collagen, that are the typical differentiated functions of osteoblasis. KCA-098 inhibited osteoclast formation in the culture of mouse bone marrow cells. These results shows that KCA-098 directly affects osteoblast to stimulate bone formation and directly inhibits osteoclast formation to inhibit bone resorption. Thereby the mineral contents of bone were inceased in organ culture experiments.In whole animal experiments.KCA-098 partially recovered the decrease of bone mineral density of the femur induced by the ovariectomy or confinement. The breaking force, the amount of force required to break the bone, was concomitantly increased by the treatment of KCA-098. These results shows that KCA-098 is effective on whole animal and applicable for the teatment of osteoporosis.

KCA-098在鸡胚骨和胎鼠骨培养中有促进骨形成和抑制骨吸收的作用，提示KCA-098是改善骨质疏松等骨疾病的有效物质。在这项工作中，我们做了两种类型的实验。我们首先设计观察KCA-098对成骨细胞（骨形成细胞）和破骨细胞（骨吸收细胞）的直接作用，以更详细地研究KCA-098对骨组织的作用机制。接下来，我们将KCA-098给予实验诱导的骨质疏松大鼠，以确定KCA-098是否可用于治疗骨质疏松症。在成骨细胞ROS 17/2.8细胞的培养中，KCA-098增加碱性磷酸酶活性和胶原蛋白的合成，这是成骨细胞的典型分化功能。KCA-098抑制小鼠骨髓细胞培养中破骨细胞的形成。这些结果表明，KCA-098直接影响成骨细胞以刺激骨形成，并直接抑制破骨细胞形成以抑制骨吸收。在整体动物实验中，KCA-098可部分恢复卵巢切除或限制所引起的股骨骨密度降低。KCA-098处理同时增加了断裂力，即断裂骨所需的力。结果表明，KCA-098对整体动物有效，适用于骨质疏松症的治疗。