Effect of diacylglycerols on osteoclastic bone resorption.

We studied the effect of various synthetic diacylglycerols (DAGs) on bone resorption by rat and chick osteoclasts. 1-stearoyl-2-arachidonoyl-sn-glycerol (DAG IV), at a concentration of 100 microM, caused a significant reduction in resorption pit number in both species at 6 and 24 hours without any toxic effect. Over a 6-hour incubation period, a significant inhibition was seen at 10 and 100 microM in both species. 1,2-dioctanoyl-sn-glycerol (DAG I) and 1,2-dihexanoyl-sn-glycerol (DAG III) caused a marked inhibition of resorption by rat osteoclasts at 6 hours, but there was recovery of bone-resorptive ability over a 24-hour incubation period. DAGs with the -rac conformation failed to have any effect on bone resorption. In time-lapse video studies, osteoclast motility was not influenced by any of the DAGs at any of the concentrations used. Our results indicate that DAGs with the -sn conformation inhibit bone resorption, and DAGs with the -rac conformation do not. The finding that DAGs, the physiological activators of protein kinase C (PKC), inhibit bone resorption provides further evidence for an important role of the PKC pathway in the regulation of osteoclast activity.