Chloroquine, hydroxystilbamidine, and dapsone inhibit resorption of fetal rat bone in organ culture

Abstract

Three potential inhibitors of lysosomal enzyme release, chloroquine, hydroxystilbamidine, and dapsone were tested for their effects on the release of previously incorporated 45Ca and beta (beta)-glucuronidase from fetal rat long bones cultured in a chemically defined medium. At concentrations of 10(-5) to 10(-8)M, all three agents were able to inhibit the stimulation of bone resorption by parathyroid hormone (PTH) or prostaglandin E2 (PGE2). Inhibition was seen at concentrations which did not alter the uptake of (3H)-2-deoxy-glucose or the incorporation of (3H)-thymidine in bone. While the inhibitors blocked the stimulation of beta-glucuronidase release by PTH and PGE2, they could also cause a direct increase in total beta-glucuronidase content and release. Hence the usual strong correlation between the release of beta-glucuronidase and 45Ca was no longer seen in the presence of inhibitors. These data indicate that chloroquine, hydroxystilbamidine, and dapsone are potent inhibitors of bone resorption which may act by blocking the release of lysosomal enzymes in cells stimulated by PTH or PGE2, but may have a different effect on other cell populations.

Cultured human monocytes and fibroblasts solubilize calcium phosphate crystals

“…Finally, the study of cellular events involved in synthetic calcium phosphate dissolution may lead to a better understanding of the mechanisms involved in the resorption of the inorganic component of bone matrix. Eilon and Raisz have previously shown that chloroquine blocks 45Ca release from parathyroid-or prostaglandin Ez-stimulated prelabeled fetal rat bone organ cultures [30].…”