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

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是一种有效的改善骨质疏松等骨病的物质。在本工作中，我们做了两种类型的实验。我们首先设计了KCA-098对骨形成细胞成骨细胞和骨吸收细胞破骨细胞的直接作用，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应用于实验性骨质疏松大鼠，以确定KCA-098是否适用于治疗骨质疏松。在成骨细胞ROS 17/2.8的培养中，KCA-098促进了成骨细胞的典型分化功能--碱性磷酸酶活性和胶原的合成。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直接作用于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。在全动物实验中，KCA-098部分恢复了卵巢切除或结扎引起的股骨骨密度的下降。破碎力，也就是折断骨头所需的力量，通过KCA-098处理而随之增加。结果表明，KCA-098对整体动物有效，适用于骨质疏松的治疗。

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.