title: Effects of ω3- and ω6-polyunsaturated fatty acids on RANKL-induced osteoclast differentiation of RAW264.7 cells: a comparative in vitro study.
abstract: Polyunsaturated fatty acids (PUFAs) have been reported to have an anabolic effect on bone in vivo, but comparative studies to identify inhibitors of osteoclast formation amongst ω3- and ω6-PUFAs are still lacking. Here we assessed the effects of the ω3-PUFAs, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) and the ω6-PUFAs, arachidonic acid (AA) and γ-linolenic acid (GLA) on a RAW264.7 osteoclast differentiation model. The effects of PUFAs on RANKL-induced osteoclast formation were evaluated by counting tartrate resistant acid phosphatase (TRAP)-positive multinucleated cells. PUFAs significantly inhibited RANKL-induced osteoclast formation in a dose-dependent manner with AA- and DHA-mediated inhibition being the strongest. Furthermore, RANKL-induced mRNA- and protein expression of the key osteoclastogenic genes cathepsin K and TRAP were inhibited by AA and more potently by DHA. Owing to the attenuated osteoclastogenesis by DHA and AA, actin ring formation and bone resorptive activity of these cells as evaluated on bone-mimetic plates were severely compromised. Hence, of the tested PUFAs, AA and DHA were found to be the most effective in inhibiting RANKL-induced osteoclast formation with the latter providing the strongest inhibitory effects. Collectively, the data indicates that these PUFAs may play an important role in regulating bone diseases characterized by excessive osteoclast activity.
authors.affiliation: Department of Physiology, University of Pretoria, Pretoria, Private Bag X323, Arcadia 0007, South Africa. christob@oncology-sa.co.za.
authors.forename: Jan C A
authors.initials: JC
authors.lastname: Boeyens
authors.affiliation: Department of Physiology, University of Pretoria, Pretoria, Private Bag X323, Arcadia 0007, South Africa. vishwa.deepak@up.ac.za.
authors.forename: Vishwa
authors.initials: V
authors.lastname: Deepak
authors.affiliation: Institute of Food, Nutrition and Human Health, Massey University, Palmerston North 4442, New Zealand. w.h.chua@massey.ac.nz.
authors.forename: Wei-Hang
authors.initials: WH
authors.lastname: Chua
authors.affiliation: Institute of Food, Nutrition and Human Health, Massey University, Palmerston North 4442, New Zealand. m.c.kruger@massey.ac.nz.
authors.forename: Marlena C
authors.initials: MC
authors.lastname: Kruger
authors.affiliation: Department of Physiology, University of Pretoria, Pretoria, Private Bag X323, Arcadia 0007, South Africa. annie.joubert@up.ac.za.
authors.forename: Annie M
authors.initials: AM
authors.lastname: Joubert
authors.affiliation: Department of Physiology, University of Pretoria, Pretoria, Private Bag X323, Arcadia 0007, South Africa. magdalena.coetzee@up.ac.za.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Coetzee
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects*; D045744:Cell Line, Tumor; D004281:Docosahexaenoic Acids / Q000494:pharmacology*; D015118:Eicosapentaenoic Acid / Q000494:pharmacology*; D043371:Fatty Acids, Omega-6 / Q000494:pharmacology*; D005260:Female; D051379:Mice; D008855:Microscopy, Electron, Scanning; D010010:Osteoclasts / Q000187:drug effects*; D053245:RANK Ligand / Q000378:metabolism*
chemical_list: D043371:Fatty Acids, Omega-6; D053245:RANK Ligand; D004281:Docosahexaenoic Acids; D015118:Eicosapentaenoic Acid