Document Detail

Long chain polyunsaturated fatty acids alter membrane-bound RANK-L expression and osteoprotegerin secretion by MC3T3-E1 osteoblast-like cells.
MedLine Citation:
PMID:  18077200     Owner:  NLM     Status:  MEDLINE    
Inflammation triggers an increase in osteoclast (bone resorbing cell) number and activity. Osteoclastogenesis is largely controlled by a triad of proteins consisting of a receptor (RANK), a ligand (RANK-L) and a decoy receptor (osteoprotegerin, OPG). Whilst RANK is expressed by osteoclasts, RANK-L and OPG are expressed by osteoblasts. The long chain polyunsaturated fatty acid (LCPUFA) arachidonic acid (AA, 20:4n-6) and its metabolite prostaglandin E2 (PGE2), are pro-inflammatory and PGE2 is a potent stimulator of RANKL expression. Various LCPUFAs such as eicosapentaenoic acid (EPA, 20:5n-3), docosahexaenoic acid (DHA, 22:6n-3) and gamma-linolenic acid (GLA, 18:3n-6) have anti-inflammatory activity. We aimed to determine if AA itself can stimulate RANKL expression and whether EPA, DHA and GLA inhibit RANKL expression in osteoblasts. MC3T3-E1/4 osteoblast-like cells were cultured under standard conditions with each of the LCPUFAs (5microg/ml) for 48h. Membrane-bound RANKL expression was measured by flow cytometry and OPG secretion measured by ELISA. In a second experiment, RANKL expression in MC3T3-E1/4 cells was stimulated by PGE2 treatment and the effect of EPA, DHA and GLA on membrane-bound RANKL expression and OPG secretion determined. The percentage of RANKL-positive cells was higher (p<0.05) than controls following treatment with AA or GLA but not after co-treatment with the cyclooxygenase inhibitor, indomethacin. DHA and EPA had no effect on membrane-bound RANKL expression under standard cell culture conditions. Secretion of OPG was lower (p<0.05) in AA-treated cells but not significantly different from controls in GLA, EPA or DHA treated cells. Treatment with prostaglandin E2 (PGE2) resulted in an increase (p<0.05) in the percentage of RANK-L positive cells and a decrease (p<0.05) in mean OPG secretion. The percentage of RANKL positive cells was significantly lower following co-treatment with PGE2 and either DHA or EPA compared to treatment with PGE2 alone. Mean OPG secretion remained lower than controls in cells treated with PGE2 regardless of co-treatment with EPA or DHA. Results from this study suggest COX products of GLA and AA induce membrane-bound RANKL expression in MC3T3-E1/4 cells. EPA and DHA have no effect on membrane-bound RANKL expression in cells cultured under standard conditions however both EPA and DHA inhibit the PGE2-induced increase in RANKL expression in MC3T3-E1/4 cells.
Raewyn C Poulsen; Frances M Wolber; Paul J Moughan; Marlena C Kruger
Publication Detail:
Type:  Journal Article     Date:  2007-11-05
Journal Detail:
Title:  Prostaglandins & other lipid mediators     Volume:  85     ISSN:  1098-8823     ISO Abbreviation:  Prostaglandins Other Lipid Mediat.     Publication Date:  2008 Feb 
Date Detail:
Created Date:  2008-01-18     Completed Date:  2008-04-29     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9808648     Medline TA:  Prostaglandins Other Lipid Mediat     Country:  United States    
Other Details:
Languages:  eng     Pagination:  42-8     Citation Subset:  IM    
Institute of Food, Nutrition and Human Health, Massey University, Private Bag 11-222, Palmerston North 4442, New Zealand.
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MeSH Terms
3T3 Cells
Cell Cycle
Cell Membrane / drug effects,  metabolism
Enzyme-Linked Immunosorbent Assay
Fatty Acids, Unsaturated / pharmacology*
Osteoblasts / drug effects*,  metabolism
Osteoprotegerin / secretion*
RANK Ligand / metabolism*
Reg. No./Substance:
0/Fatty Acids, Unsaturated; 0/Osteoprotegerin; 0/RANK Ligand; 0/Tnfsf11 protein, mouse

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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