|Budget Amount *help
¥2,100,000 (Direct Cost : ¥2,100,000)
Fiscal Year 1990 : ¥500,000 (Direct Cost : ¥500,000)
Fiscal Year 1989 : ¥1,600,000 (Direct Cost : ¥1,600,000)
It is important to study on the age-related mechanism to cause osteoporosis and on the medical treatment for it, as well as to study on senile dementia occurring among increasingly aged persons.
In recent years, several investigators have demonstrated that bone metabolism is regulated with various kinds of hormones and autacoids, which have multitudious effects in a small amount. We have been studying a intriguing regulation mechanism of bone formation by prostaglandins. Meanwhile we recently found that prostaglandin D_2 stimulates mineralization in cultured human osteoblasts, and then have the interesting results on stimulation mechanism, demonstrating for these two years as follows.
1) Prostaglandin D_2 in culture medium is found to be converted to ^<12>*-prostaglandin J_2 with serum albumin. Finally the active form has identified as ^<12>*-prostaglandin J_2. Cyclopentenon ring of the compound is essential to give the effect, but C-15 hydroxy is not, as the experimental results that various kinds of derivatives have been used to clarify the effect.
2) ^<12>*-prostaglandin J_2 actually increases calcium ion influx into cells, participating in the mechanism on mineralization. The treatment with ^<12>*-prostagladin J_2 for 20 days increases miniralization by 2-3 folds.
3) The mineralizaion is based on bone collagen. It depends on an enhanced expression of collagen genes, demonstrating by the northern blot analysis for procollagen alpha^1 (I) mRNA.
4) Osteocalsin, a non-collagenous protein, physiologically active in bone metabolism, is not affected on its release from cells, when ^<12>*-prostaglandin J_2 is added. However, Its accumulaton in cells is increased as well as an active form of vitamin D_3.
5) Presumably, ^<12>*-prostaglandin J_2 directly penetrates into cells without specific receptor(s), since it does not affect on intracellular CAMP level.
Further functions of prostaglandins involving the age-related metabolism in bone should be examined by causal analyses.