Koshihara Y, Takamori R, Nomura K, Sugiura S, Kurozumi S
Department of Pharamacology, Tokyo Metropolitan Institute of Gerontology, Japan.
J Pharmacol Exp Ther. 1991 Sep;258(3):1120-6.
Human osteoblasts derived from long bone periosteum were induced to mineralize in culture in the presence of 2 mM alpha-glycerophosphate, with typical characteristics of mineralization, namely, accumulation of hydroxyapatite and increases in alkaline phosphatase activity and in osteocalcin production. Mineralization was also enhanced by 10(-8) M 1 alpha, 25-dihydroxyvitamin D3. In this system, a prostaglandin A1 derivative, TEI-3313, with the chemical structure 5-[(Z,2E)-4,7-dihydroxy-2-heptenyridene]-4-hydroxy-2-methylthio-4- (4- phenoxybutyl)-2-cyclopentenone, was found to enhance mineralization as effectively as 1 alpha, 25-dihydroxyvitamin D3, although its potency was 10 times lower than that of the vitamin D3 metabolite. Osteocalcin, a bone-specific noncollagenous matrix protein, accumulated onto the cell layers by treatment with TEI-3313 to a much greater extent than those released into the culture medium. TEI-3313 also enhanced collagen synthesis. Based on the finding that TEI-3313 enhanced the synthesis of both collagen and noncollagenous protein, it is speculated that TEI-3313 enhanced the mineralization by stimulating the expression of various genes in osteoblasts.
源自长骨骨膜的人成骨细胞在2 mMα-甘油磷酸存在的情况下于培养中被诱导矿化，具有典型的矿化特征，即羟基磷灰石的积累以及碱性磷酸酶活性和骨钙素产生的增加。10(-8) M的1α,25-二羟基维生素D3也增强了矿化作用。在该系统中，发现一种前列腺素A1衍生物TEI-3313，其化学结构为5-[(Z,2E)-4,7-二羟基-2-庚烯叉基]-4-羟基-2-甲硫基-4-(4-苯氧基丁基)-2-环戊烯酮，尽管其效力比维生素D3代谢物低10倍，但能像1α,25-二羟基维生素D3一样有效地增强矿化作用。骨钙素是一种骨特异性非胶原蛋白基质蛋白，通过用TEI-3313处理，其在细胞层上的积累程度远大于释放到培养基中的程度。TEI-3313还增强了胶原蛋白的合成。基于TEI-3313增强胶原蛋白和非胶原蛋白合成这一发现，则推测TEI-3313通过刺激成骨细胞中各种基因的表达来增强矿化作用。
