title: The effects of polyunsaturated fatty acids and their metabolites on osteoclastogenesis in vitro.
abstract: Bone homeostasis is maintained by active remodeling through the balance between resorption (by osteoclasts) and synthesis (by osteoblasts). In this study, we examined the effects of polyunsaturated fatty acids (PUFAs) and their metabolites on sRANKL-induced differentiation of bone marrow-derived macrophages (BMMs) into osteoclasts in vitro. Docosahexaenoic acid (DHA) strongly inhibited osteoclastogenesis; however, dihomo-gamma-linolenic acid (DGLA), arachidonic acid (AA) and eicosapentaenoic acid (EPA) enhanced it. The enhancement effect of PUFAs on osteoclastogenesis was mediated predominantly by cyclooxygenase (COX) products, because the effect was inhibited by a COX inhibitor. It was also found that COX products of PUFAs, prostaglandin E(1), E(2), and E(3), clearly increased in osteoclastogenesis. The inhibitory effect of DHA on osteoclastogenesis was reversed by treatment with a lipoxygenase (LOX) inhibitor. Furthermore, resolvin D1, a LOX product of DHA, significantly inhibited osteoclastogenesis. Quantitative analysis of specific mRNA levels revealed that DHA-mediated attenuation of osteoclastogenesis might be due to a decrease in DC-STAMP expression. These results suggested that the effect of DHA on osteoclastogenesis is, at least in part, mediated by lipoxygenase products. This study showed a distinct mechanism of the effect of PUFAs on osteoclastogenesis and will provide evidence for therapeutic treatment with DHA in osteoporotic patients.
authors.affiliation: Department of Cellular Physiological Chemistry, Graduate School, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8549, Japan.
authors.forename: Jizhong
authors.initials: J
authors.lastname: Yuan
authors.forename: Masako
authors.initials: M
authors.lastname: Akiyama
authors.forename: Ken-ichi
authors.initials: K
authors.lastname: Nakahama
authors.forename: Takahiro
authors.initials: T
authors.lastname: Sato
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Uematsu
authors.forename: Ikuo
authors.initials: I
authors.lastname: Morita
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004281:Docosahexaenoic Acids / Q000378:metabolism / Q000494:pharmacology; D005231:Fatty Acids, Unsaturated / Q000378:metabolism* / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects; D008084:Lipoxygenase / Q000378:metabolism; D008297:Male; D051379:Mice; D010010:Osteoclasts / Q000166:cytology* / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D011458:Prostaglandins E / Q000378:metabolism / Q000494:pharmacology
chemical_list: D015415:Biomarkers; D016861:Cyclooxygenase Inhibitors; D005231:Fatty Acids, Unsaturated; D011458:Prostaglandins E; C518399:resolvin D1; D004281:Docosahexaenoic Acids; D008084:Lipoxygenase