Journal
EUROPEAN JOURNAL OF PHARMACOLOGY
Volume 450, Issue 1, Pages 11-17Publisher
ELSEVIER
DOI: 10.1016/S0014-2999(02)02040-X
Keywords
S12911-2; osteoclast; bone resorption; differentiation
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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 Sr2+, 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 Sr2+ to 66% at 10(-3) M Sr2+ (P<0.05 in each case). A continuous incubation (10(-3) M Sr2+) 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. (c) 2002 Elsevier Science B.V. All rights reserved.
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