Role of protein kinase C (PKC) in bone resorption: effect of the specific PKC inhibitor 1-alkyl-2-methylglycerol.
The specific inhibitor of protein kinase C, 1-O-alkyl-2-O-methylglycerol (AMG), was studied for its effect on bone resorption, measured as 45Ca-release, in fetal mouse calvariae. AMG (1 to 50 microM) had no effect on basal bone resorption. AMG inhibited parathyroid hormone (40 nM) induced bone resorption in a dose-dependent manner. Resorption induced by 1,25 (OH)2-vitamin D3 (10 nM) or prostaglandin E2 (5 microM) was also inhibited by AMG. The release of beta-glucuronidase activity paralleled the course of the 45Ca-release. The production of interleukin 6, induced by parathyroid hormone, in fetal rat calvarial osteoblasts was not affected by AMG. AMG (1 to 50 microM) had no cytotoxic effects on cells or calvariae. From these results it is concluded that protein kinase C may have an important role in the regulation of bone resorption.
Bos
M P
MP
Laboratory of Cell Biology and Histology, University of Leiden, Rijnsburgerweg, The Netherlands.
Most
W
W
van Leeuwen
J P
JP
Herrmann-Erlee
M P
MP
D001862:Bone Resorption; D001842:Bone and Bones / Q000187:drug effects / Q000502:physiology; D002117:Calcitriol / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D015232:Dinoprostone / Q000494:pharmacology; D005333:Fetus; D005966:Glucuronidase / Q000378:metabolism; D005995:Glyceryl Ethers / Q000494:pharmacology*; D015850:Interleukin-6 / Q000378:metabolism; D009924:Organ Culture Techniques; D010006:Osteoblasts / Q000187:drug effects / Q000502:physiology*; D010281:Parathyroid Hormone / Q000494:pharmacology; D010446:Peptide Fragments / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism*; D019379:Teriparatide
D005995:Glyceryl Ethers; D015850:Interleukin-6; D010281:Parathyroid Hormone; D010446:Peptide Fragments; D019379:Teriparatide; D011493:Protein Kinase C; D005966:Glucuronidase; D002117:Calcitriol; D015232:Dinoprostone; D002118:Calcium