Physiological and pathological analysis of BMP-3b in cardiovascular system.

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BMP-3b was originally isolated from femur and have antagonistic activity against BMP-2 in osteoblast and developing embryos. Although BMP-3b gene was highly expressed in aorta, its function in cardiovascular system is still unknown. Regarding the BMPs function in that system, it has been now active and being progress since the paper which reported that mutation of BMP receptor caused PPH was published in 2000. To clarify the function of BMP-3b in cardiovascular system, we first examined the effect of that in cultured aortic smooth muscle cells. BMP-3b gene was expressed in both in rat and human cells and level of that was changed by the preparation method(enzyme and explant method) . The biological activity was examined by adenovirus over-expression system. The result showed that BMP-3b had growth inhibitory effect. During cloning of the intrinsic form of BMP-3b in these cells, we isolated new splicing variant that was never known. In this new variant, essential part of BMP-3b activity of the protein was deleted, suggesting that there would be novel activity and molecular form of BMP-3b. Next, we examined the function of BMP-Sb in the heart. In the cultured cells from neonatal rat, BMP-3b gene was expressed both in myocyte and non-myocyte cells. In the developing stage of the heart(embryo d8.5 to d10.5), BMP-3b gene expression was observed through the entire stage and the level increased with stage. In addition, we have just generated TG mice overexpressing BMP-3b especially in heart, BMP-3b expression level was 10 to 100 times higher than wild ones in heart. Now we are breeding and examining these mice. We developed antibody specific for BMP-3b and investigated the molecular form of BMP-3b. We found that the molecular form of secreted BMP-3b was unique that was never reported in BMP family, so we are now checking the molecular form in rat tissues where BMP-3b was highly expressed.