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.
Moonga
B S
BS
Regional Bone Center, Helen Hayes Hospital, New York State Department of Health, Route 9W, West Haverstraw, New York 10993, USA.
Stein
L S
LS
Kilb
J M
JM
Dempster
D W
DW
D000704:Analysis of Variance; D000818:Animals; D001862:Bone Resorption / Q000188:drug therapy* / Q000201:enzymology; D002465:Cell Movement / Q000187:drug effects; D002470:Cell Survival; D002642:Chick Embryo; D002645:Chickens; D004075:Diglycerides / Q000494:pharmacology / Q000627:therapeutic use*; D004789:Enzyme Activation / Q000187:drug effects; D010010:Osteoclasts / Q000166:cytology / Q000187:drug effects*; D011493:Protein Kinase C / Q000378:metabolism*; D051381:Rats; D013237:Stereoisomerism
D004075:Diglycerides; D011493:Protein Kinase C