Impact of docosahexaenoic acid on gene expression during osteoclastogenesis in vitro--a comprehensive analysis.
Polyunsaturated fatty acids (PUFAs), especially n-3 polyunsaturated fatty acids, docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), are known to protect against inflammation-induced bone loss in chronic inflammatory diseases, such as rheumatoid arthritis, periodontitis and osteoporosis. We previously reported that DHA, not EPA, inhibited osteoclastogenesis induced by the receptor activator of nuclear factor-κB ligand (sRANKL) in vitro. In this study, we performed gene expression analysis using microarrays to identify genes affected by the DHA treatment during osteoclastogenesis. DHA strongly inhibited osteoclastogenesis at the late stage. Among the genes upregulated by the sRANKL treatment, 4779 genes were downregulated by DHA and upregulated by the EPA treatment. Gene ontology analysis identified sets of genes related to cell motility, cell adhesion, cell-cell signaling and cell morphogenesis. Quantitative PCR analysis confirmed that DC-STAMP, an essential gene for the cell fusion process in osteoclastogenesis, and other osteoclast-related genes, such as Siglec-15, Tspan7 and Mst1r, were inhibited by DHA.
Department of Cellular Physiological Chemistry, Graduate School, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8549, Japan.
Masako
M
Akiyama
Ken-ichi
K
Nakahama
Ikuo
I
Morita
D000818:Animals; D001862:Bone Resorption / Q000378:metabolism*; D002448:Cell Adhesion / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D004281:Docosahexaenoic Acids / Q000494:pharmacology*; D015536:Down-Regulation; D015118:Eicosapentaenoic Acid / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects*; D020869:Gene Expression Profiling; D007136:Immunoglobulins / Q000235:genetics / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D051379:Mice; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D010010:Osteoclasts / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D053245:RANK Ligand / Q000235:genetics / Q000378:metabolism; D020794:Receptor Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D015854:Up-Regulation
C499636:DC-STAMP protein, mouse; D007136:Immunoglobulins; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D053245:RANK Ligand; C582874:Siglec-15 protein, mouse; C403502:Tm4sf2 protein, mouse; D004281:Docosahexaenoic Acids; D015118:Eicosapentaenoic Acid; C080835:RON protein; D020794:Receptor Protein-Tyrosine Kinases