Inhibition of osteoclastic motility by prostaglandins I2, E1, E2 and 6-oxo-E1.
We have recently found that calcitonin (CT), a hormone which inhibits osteoclastic bone resorption, completely abolishes the normally intense cytoplasmic motility of isolated osteoclasts. Here we report that prostaglandin (PG)I2, PGE1, PGE2 and 6-oxo-PGE1 cause an identical change in behaviour to that induced by CT. The order of potency was PGI2 greater than PGE1 greater than 6-oxo-PGE1 greater than PGE2. We found that, unlike CT which causes prolonged immotility in osteoclasts, the effect of these PGs was transient. The transient nature of the inhibition was not caused by their decay or inactivation, nor was it due to production in the cultures of a stimulator of osteoclast motility. Osteoclasts refractory to one PG were also less sensitive to the others, but showed no loss of sensitivity to CT, suggesting that the PGs share a common receptor system, distinct from that for CT. The PGs, like CT, appear to operate by increasing the cyclic AMP level in osteoclasts. The identical nature of the response of osteoclasts to PGs and CT, and the shared use of cyclic AMP as second messenger, suggest that the PGs, like CT, act directly on osteoclasts to inhibit bone resorption by these cells. Osteoblasts are known to make PGs, and we suggest that osteoblasts make them as agents of the local control of osteoclastic bone resorption. Paradoxically, when PGs are added to bone in organ culture they stimulate bone resorption. Like PTH they increase osteoblastic cyclic AMP levels, and the effect of adding PGs to bone may be a transient direct inhibition of osteoclasts followed by a sustained PTH-like stimulation of osteoclasts through osteoblasts. This mechanism may account for the bone resorption seen in inflammatory and malignant disease.
D000527:Alprostadil / Q000031:analogs & derivatives; D000818:Animals; D002465:Cell Movement / Q000187:drug effects; D002478:Cells, Cultured; D003864:Depression, Chemical; D015232:Dinoprostone; D004305:Dose-Response Relationship, Drug; D011464:Epoprostenol / Q000494:pharmacology; D010010:Osteoclasts / Q000187:drug effects* / Q000502:physiology; D011453:Prostaglandins / Q000494:pharmacology*; D011458:Prostaglandins E / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013997:Time Factors
D011453:Prostaglandins; D011458:Prostaglandins E; C022950:6-ketoprostaglandin E1; D011464:Epoprostenol; D000527:Alprostadil; D015232:Dinoprostone