QUANTITATIVE STUDIES ON THE EFFECT OF PROSTACYCLIN ON FRESHLY ISOLATED RAT OSTEOCLASTS IN CULTURE

Prostaglandins exert marked but transient inhibitory effects on bone r esorption. The present study examines the effects of prostacyclin (0.1 5 to 25 mu M) on the morphology of freshly disaggregated rat osteoclas ts. An area descriptor, rho, represented changes in total cell spread area, and a motility descriptor, mu, represented overall changes in ce ll motility. The application of prostacyclin intercepted the trend of an increasing cell spread area with time and produced a transient redu ction of rho, an R effect. Its magnitude depended upon concentration a nd was marked at 25 mu M prostacyclin. The subsequent recovery (+0.8/m in) of rho at this concentration resembled the persistent spreading se en in the absence of the agonist. There was also a sustained decrease in mu to approximately 60% of its pretreatment value (a Q effect) foll owing the application of 25 mu M prostacyclin. The extracellular appli cation of 20 mM [Ca2+] produced a similarly transient cell retraction preceded by a rise of cytosolic [Ca2+], but without a corresponding de crease in mu. In contrast, prostacyclin did not elevate cytosolic [Ca2 +], suggesting the triggering of an alternative transduction pathway. A fully reversible retraction together with incomplete quiescence may explain the transience characteristic of the antiresorptive action of prostacyclin.