EFFECT OF DIACYLGLYCEROLS ON OSTEOCLASTIC BONE-RESORPTION

We studied the effect of various synthetic diacylglycerols (DAGs) on b one resorption by rat and chick osteoclasts. 1-stearoyl-2-arachidonoyl -sn-glycerol (DAG IV), at a concentration of 100 mu M, caused a signif icant reduction in resorption pit number in both species at 6 and 24 h ours without any toxic effect. Over a 6-hour incubation period, a sign ificant inhibition was seen at 10 and 100 mu M in both species. 1,2-di octanoyl-sn-glycerol (DAG I) and 1, 2-dihexanoyl-sn-glycerol (DAG III) caused a marked inhibition of resorption by rat osteoclasts at 6 hour s, but there was recovery of bone-resorptive ability over a 24-hour in cubation period. DAGs with the -rac conformation failed to have any ef fect on bone resorption. In time-lapse video studies, osteoclast motil ity was not influenced by any of the DAGs at any of the concentrations used. Our results indicate that DAGs with the -sn conformation inhibi t bone resorption, and DAGs with the -rac conformation do not. The fin ding that DAGs, the physiological activators of protein kinase C (PKC) , inhibit bone resorption provides further evidence for an important r ole of the PKC pathway in the regulation of osteoclast activity.