In vitro effects of S12911-2 on osteoclast function and bone marrow macrophage differentiation.
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.
Baron
Roland
R
Department of Cell Biology, Yale University School of Medicine, 333 Cedar Street, IE 55 SHM, New Haven, CT 06510, USA.
Tsouderos
Yannis
Y
D000704:Analysis of Variance; D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D001862:Bone Resorption / Q000517:prevention & control; D002117:Calcitriol / Q000494:pharmacology; D002120:Calcium Channel Agonists / Q000494:pharmacology; D024402:Carbonic Anhydrase II / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D002454:Cell Differentiation / Q000187:drug effects*; D002478:Cells, Cultured; D002645:Chickens; D004305:Dose-Response Relationship, Drug; D004797:Enzyme-Linked Immunosorbent Assay; D066298:In Vitro Techniques; D039302:Integrin alphaVbeta3 / Q000096:biosynthesis; D008264:Macrophages / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D009942:Organometallic Compounds / Q000494:pharmacology*; D010010:Osteoclasts / Q000166:cytology / Q000187:drug effects*; D051381:Rats; D013876:Thiophenes / Q000494:pharmacology*
D002120:Calcium Channel Agonists; D039302:Integrin alphaVbeta3; D009942:Organometallic Compounds; D013876:Thiophenes; C081587:strontium ranelate; D024402:Carbonic Anhydrase II; D002117:Calcitriol