title: Effects of arachidonic acid, docosahexaenoic acid, prostaglandin E(2) and parathyroid hormone on osteoprotegerin and RANKL secretion by MC3T3-E1 osteoblast-like cells.
abstract: Bone is continuously remodeled through resorption by osteoclasts and the subsequent synthesis of the bone matrix by osteoblasts. Cell-to-cell contact between osteoblasts and osteoclast precursors is required for osteoclast formation. RANKL (receptor activator of nuclear factor-kappaB ligand) expressed on osteoblastic cell membranes stimulates osteoclastogenesis, while osteoprotegerin (OPG) secreted by osteoblasts inhibits osteoclastogenesis. Although polyunsaturated fatty acids (PUFAs) have been implicated in bone homeostasis, the effects thereof on OPG and RANKL secretion have not been investigated. MC3T3-E1 osteoblasts were exposed to the n-6 PUFA arachidonic acid (AA) and the n-3 PUFA docosahexaenoic acid (DHA); furthermore, the bone-active hormone parathyroid hormone (PTH) and the effects thereof were tested on OPG and RANKL secretion. Prostaglandin E(2) (PGE(2)), a product of AA metabolism that was previously implicated in bone homeostasis, was included in the study. AA (5.0-20 microg/ml) inhibited OPG secretion by 25-30%, which was attenuated by pretreatment with the cyclooxygenase blocker indomethacin, suggesting that the inhibitory effect of AA on OPG could possibly be PGE(2)-mediated. MC3T3-E1 cells secreted very low basal levels of RANKL, but AA stimulated RANKL secretion, thereby decreasing the OPG/RANKL ratio. DHA suppressed OPG secretion to a smaller extent than AA. This could, however, be due to endogenous PGE(2) production. No RANKL could be detected after exposing the MC3T3-E1 cells to DHA. PTH did not affect OPG secretion, but stimulated RANKL secretion. This study demonstrates that AA and PTH reduce the OPG/RANKL ratio and may increase osteoclastogenesis. DHA, however, had no significant effect on OPG or RANKL in this model.
authors.affiliation: Department of Physiology, University of Pretoria, PO Box 2034, Pretoria 0001, South Africa. magdalena.coetzee@up.ac.za
authors.forename: Magdalena
authors.initials: M
authors.lastname: Coetzee
authors.forename: Marianne
authors.initials: M
authors.lastname: Haag
authors.forename: Marlena C
authors.initials: MC
authors.lastname: Kruger
mesh_terms: D000818:Animals; D016718:Arachidonic Acid / Q000494:pharmacology*; D002460:Cell Line; D017077:Culture Media, Conditioned / Q000737:chemistry; D015232:Dinoprostone / Q000494:pharmacology; D004281:Docosahexaenoic Acids / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D010006:Osteoblasts / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D053244:Osteoprotegerin / Q000378:metabolism*; D010281:Parathyroid Hormone / Q000494:pharmacology*; D053245:RANK Ligand / Q000378:metabolism*
chemical_list: D017077:Culture Media, Conditioned; D053244:Osteoprotegerin; D010281:Parathyroid Hormone; D053245:RANK Ligand; C505689:Tnfsf11 protein, mouse; D004281:Docosahexaenoic Acids; D016718:Arachidonic Acid; D015232:Dinoprostone