1996 Fiscal Year Final Research Report Summary
Development of medicine for osteoporosis --- The effect of a new chemically-synthesized substance, KCA-098, on the melabolism of the bone
| Project/Area Number |
07672385
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Biological pharmacy
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| Research Institution | Teikyo University |
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Principal Investigator |
KAWASHIMA Kohtaro Dept.of Pharm Sci.Teikyo University Professor, 薬学部, 教授 (20124993)
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| Project Period (FY) |
1995 – 1996
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| Keywords | Medicine for osteoporosis / KCA-098 / Osteoblast / Osteoclast / Alkaline phosphatase / Osteocalcin |
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| Research Abstract |
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.
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