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

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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), 6α-carbaprostaglandin I2 (C-PGI2), a carbon substituted analog of PGI2, and salmon calcitonin (CT) on the release of previously incorporated45Ca 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 in45Ca 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 medium45Ca of 21% at 1 and 2 hours. Medium calcium measurements suggest that the change in45Ca 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. Moreover, the addition of PGI2 (10−5M) to PTH-treated cultures actually enhanced45Ca release beginning to 6 hours, when PGI2 alone had no effect upon bone resorption. These results confirm that high concentration of PGI2 can stimulate bone resorption and show a similar response to a stable analog, C-PGI2. Moreover, PGI2 was found to enhance PTH-stimulated bone resorption. A small transient inhibition of45Ca release was observed with a high concentration of PGE1 (10−5M) in the absence of PTH, which could be due to a transient direct inhibitory action upon osteoclasts.