RRC ID 73036
Author Tintut Y, Parhami F, Tsingotjidou A, Tetradis S, Territo M, Demer LL.
Title 8-Isoprostaglandin E2 enhances receptor-activated NFkappa B ligand (RANKL)-dependent osteoclastic potential of marrow hematopoietic precursors via the cAMP pathway.
Journal J Biol Chem
Abstract Lipid oxidation products promote atherosclerosis and may also affect osteoporosis. We showed previously that oxidized lipids including 8-isoprostaglandin E2 (isoPGE2) inhibit osteoblastic differentiation of preosteoblasts. Since osteoporosis is mediated both by decreased osteoblastic bone formation and by increased osteoclastic bone resorption, we assessed whether oxidized lipids regulate the osteoclastic potential of marrow hematopoietic cells. Treatment of marrow-derived preosteoclasts with isoPGE2 enhanced osteoclastic differentiation as evidenced by increased tartrate-resistant acid phosphatase (TRAP) activity and multinucleation, which were inhibited by calcitonin, and increased numbers of resorption pits. The enhanced osteoclastic differentiation by isoPGE2 was observed whether preosteoclasts were in coculture with stromal cells or in monoculture in the presence of receptor-activated NFkappaB ligand (RANKL) and macrophage colony-stimulating factor. Receptor antagonist studies suggest that isoPGE2 effects were mediated by prostaglandin receptor subtypes EP2/DP on preosteoclasts and subtype EP1 and thromboxane receptors on stromal/osteoblast cells. The enhanced TRAP activity was also inhibited by cAMP-dependent protein kinase inhibitors, and isoPGE2 elevated intracellular cAMP levels of preosteoclast monocultures. Other oxidized lipids also enhanced the TRAP activity of preosteoclast monocultures. These data suggest that isoPGE2 enhances osteoclastic differentiation of marrow preosteoclasts and that this regulation occurs via the cAMP-dependent protein kinase pathway.
Volume 277(16)
Pages 14221-6
Published 2002-4-19
DOI 10.1074/jbc.M111551200
PII S0021-9258(19)61030-6
PMID 11827970
MeSH Actins / metabolism Animals Bone Marrow Cells Calcitonin / metabolism Carrier Proteins / metabolism* Cell Differentiation Cell Line Cells, Cultured Coculture Techniques Cyclic AMP / metabolism* Cyclic AMP-Dependent Protein Kinases / metabolism Dinoprostone / analogs & derivatives Dinoprostone / pharmacology* Isoprostanes / pharmacology* Lipid Metabolism Membrane Glycoproteins / metabolism* Mice Mice, Inbred C57BL Microscopy, Phase-Contrast Osteoclasts / metabolism* Osteoporosis / metabolism Oxygen / metabolism RANK Ligand Receptor Activator of Nuclear Factor-kappa B Vasoconstrictor Agents / pharmacology
IF 4.238
Human and Animal Cells ST2(RCB0224)