Effects of prostacyclin and prostaglandin E1 (PGE1) on bone resorption in the presence and absence of parathyroid hormone

Abstract

Prostaglandins have been shown to stimulate osteoclastic bone resorption in organ culture but morphologic studies of isolated osteoclasts have shown a transient calcitonin-like inhibiting effect of these agents. We looked for a dual effect on bone resorption by comparing the early and late effects of prostaglandin E1 (PGE1), prostacyclin (PGI2), 6 alpha-carbaprostaglandin I2 (C-PGI2), a carbon substituted analog of PGI2, and salmon calcitonin (CT) on the release of previously incorporated 45Ca from fetal rat long bones cultured in the presence of an inhibitor of cyclooxygenase, RO-20-5720. Experiments were performed in both the presence and absence of PTH (400 ng/ml), which was administered 24 hours before addition of prostaglandins or CT. In control cultures not stimulated by PTH, CT (100 mU/ml) produced significant decreases in 45Ca release at 48, 72, and 96 hours while PGE1 (10(-6) M), PGI2 (10(-5)), and C-PGI2 (10(-6) M) each produced significant increases in resorption at 24 through 96 hours. PGE1 at 10(-5) M, but not 10(-6) M, caused a significant decrease in medium 45Ca of 21% at 1 and 2 hours. Medium calcium measurements suggest that the change in 45Ca was due to inhibition of release and not to increased uptake. PGI2 (10(-5) M) and C-PGI2 (10(-6) M) caused no significant inhibitory effect. In cultures stimulated by PTH, CT produced significant inhibition of bone resorption of 6 through 96 hours, but no inhibition of bone resorption was noted at either early or late time points with PGE1, PGI2, or C-PGI2.(ABSTRACT TRUNCATED AT 250 WORDS)