Baron Roland, Tsouderos Yannis
Department of Cell Biology, Yale University School of Medicine, 333 Cedar Street, IE 55 SHM, New Haven, CT 06510, USA.
Eur J Pharmacol. 2002 Aug 16;450(1):11-7. doi: 10.1016/s0014-2999(02)02040-x.
In order to determine whether 5-[bis(carboxymethyl) amino]-2-carboxy4-cyano-3-thiopheneacetic acid distrontium salt (S12911-2) inhibits bone resorption by acting on the differentiation and/or function of osteoclasts, its effects were assessed on the 1,25-dihydroxyvitamin D(3)-induced expression of carbonic anhydrase II and vitronectin receptor in chicken bone marrow cells, and on the resorbing activity of authentic rat osteoclasts cultured on bone slices. S12911-2 dose-dependently inhibited, after a 6-day exposure, the expression of carbonic anhydrase II and vitronectin receptor in stimulated osteoclasts (46% and 40%, respectively, at 10(-3) M Sr(2+), P<0.05). A pre-incubation of bone slices with S12911-2 induced a dose-dependent inhibition of bone resorbing activity from 32% at 10(-4) M Sr(2+) to 66% at 10(-3) M Sr(2+) (P<0.05 in each case). A continuous incubation (10(-3) M Sr(2+)) induced a greater inhibition of bone resorbing activity (73%, P<0.05). The inhibition of bone resorption obtained specifically with S12911-2 is related to an inhibition of the differentiation and resorbing activity of the osteoclasts.
为了确定5-[双（羧甲基）氨基]-2-羧基-4-氰基-3-噻吩乙酸二锶盐（S12911-2）是否通过作用于破骨细胞的分化和/或功能来抑制骨吸收，研究了其对1,25-二羟基维生素D(3)诱导鸡骨髓细胞中碳酸酐酶II和玻连蛋白受体表达的影响，以及对在骨切片上培养的原代大鼠破骨细胞吸收活性的影响。经6天暴露后，S12911-2呈剂量依赖性抑制受刺激破骨细胞中碳酸酐酶II和玻连蛋白受体的表达（在10(-3) M Sr(2+)时分别为46%和40%，P<0.05）。用S12911-2预孵育骨切片可诱导骨吸收活性呈剂量依赖性抑制，从10(-4) M Sr(2+)时的32%到10(-3) M Sr(2+)时的66%（每种情况P<0.05）。持续孵育（10(-3) M Sr(2+)）诱导对骨吸收活性的更大抑制（73%，P<0.05）。用S12911-2特异性获得的骨吸收抑制与破骨细胞的分化和吸收活性抑制有关。
