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S 12911‐2 Inhibits Osteoclastic Bone Resorption In Vitro
Author(s) -
Takahashi N,
Sasaki T,
Tsouderos Y,
Suda T
Publication year - 2003
Publication title -
journal of bone and mineral research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.882
H-Index - 241
eISSN - 1523-4681
pISSN - 0884-0431
DOI - 10.1359/jbmr.2003.18.6.1082
Subject(s) - osteoclast , resorption , bone resorption , chemistry , in vitro , fetus , endocrinology , medicine , basal (medicine) , biology , biochemistry , pregnancy , genetics , insulin
The potential anti‐osteoporotic activity of the strontium compound, S12911, was tested on osteoclast‐like cells and on cultured fetal mouse long bones. From 1 mM Sr 2+ , S12911 reduced both basal and stimulated bone resorption by decreasing osteoclast activity and ruffled border formation. The aim of this study was to evaluate the effects of S 12911‐2 on osteoclastic bone resorption using in vitro systems. Osteoclast‐like cells, produced in vitro by co‐culture of mouse bone marrow cells with primary osteoblasts, were allowed to settle on dentine slices, and the area of resorption pits formed after 48 h was measured using an image analysis system. S 12911‐2, at a minimal active concentration of 1 mM Sr 2+ , significantly reduced pit formation by these cells ( p < 0.05). Pretreatment of slices for 48 h with S 12911‐2 (5 mM Sr 2+ ) did not produce appreciable inhibition of resorption. Bone resorption in cultured fetal mouse long bones was assessed by measuring the release of pre‐incorporated 45 calcium. S 12911‐2 inhibited resorption in control cultures (18.9%, p ≤ 0.05) and in bones cultured with the active form of vitamin D 3 [1,25(OH) 2 D 3 ] (44.5%, p ≤ 0.05). S 12911‐2 had no effect on the number of osteoclasts observed histochemically in longitudinal sections prepared from fetal mouse long bones. Electron microscopy of mouse long bones treated with S 12911‐2 (3 mM Sr 2+ ) showed osteoclasts with clear zones facing the bone surface, but without well‐developed ruffled borders; untreated bones contained osteoclasts with normal ruffled borders. These results indicate that S 12911‐2 inhibits osteoclast activity. This effect is directly linked to the presence of strontium, is effective on basal and stimulated resorption, and involves a decrease in ruffled border formation by osteoclasts.