Sun Dongxu, Krishnan Aparna, Zaman Khaliquz, Lawrence Richard, Bhattacharya Arunabh, Fernandes Gabriel
Department of Medicine, Division of Clinical Immunology, University of Texas Health Science Center at San Antonio, San Antonio, Texas 78229-3900, USA.
J Bone Miner Res. 2003 Jul;18(7):1206-16. doi: 10.1359/jbmr.2003.18.7.1206.
UNLABELLED: The mechanisms of action of dietary fish oil (FO) on osteoporosis are not fully understood. This study showed FO decreased bone loss in ovariectomized mice because of inhibition of osteoclastogenesis. This finding supports a beneficial effect of FO on the attenuation of osteoporosis. INTRODUCTION: Consumption of fish or n-3 fatty acids protects against cardiovascular and autoimmune disorders. Beneficial effects on bone mineral density have also been reported in rats and humans, but the precise mechanisms involved have not been described. METHODS: Sham and ovariectomized (OVX) mice were fed diets containing either 5% corn oil (CO) or 5% fish oil (FO). Bone mineral density was analyzed by DXA. The serum lipid profile was analyzed by gas chromatography. Receptor activator of NF-kappaB ligand (RANKL) expression and cytokine production in activated T-cells were analyzed by flow cytometry and ELISA, respectively. Osteoclasts were generated by culturing bone marrow (BM) cells with 1,25(OH)2D3. NF-kappaB activation in BM macrophages was measured by an electrophoretic mobility shift assay. RESULTS AND CONCLUSION: Plasma lipid C16:1n6, C20:5n3, and C22:6n3 were significantly increased and C20:4n6 and C18:2n6 decreased in FO-fed mice. Significantly increased bone mineral density loss (20% in distal left femur and 22.6% in lumbar vertebrae) was observed in OVX mice fed CO, whereas FO-fed mice showed only 10% and no change, respectively. Bone mineral density loss was correlated with increased RANKL expression in activated CD4+ T-cells from CO-fed OVX mice, but there was no change in FO-fed mice. Selected n-3 fatty acids (docosahexaenoic acid [DHA] and eicosapentaenoic acid [EPA]) added in vitro caused a significant decrease in TRACP activity and TRACP+ multinuclear cell formation from BM cells compared with selected n-6 fatty acids (linoleic acid [LA] and arachidonic acid [AA]). DHA and EPA also inhibited BM macrophage NF-kappaB activation induced by RANKL in vitro. TNF-alpha, interleukin (IL)-2, and interferon (IFN)-gamma concentrations from both sham and OVX FO-fed mice were decreased in the culture medium of splenocytes, and interleukin-6 was decreased in sham-operated FO-fed mice. In conclusion, inhibition of osteoclast generation and activation may be one of the mechanisms by which dietary n-3 fatty acids reduce bone loss in OVX mice.
未标记：膳食鱼油（FO）对骨质疏松症的作用机制尚未完全了解。本研究表明，FO可减少去卵巢小鼠的骨质流失，因为它能抑制破骨细胞生成。这一发现支持了FO对减轻骨质疏松症具有有益作用。 引言：食用鱼类或n-3脂肪酸可预防心血管疾病和自身免疫性疾病。在大鼠和人类中也报道了对骨矿物质密度的有益影响，但具体机制尚未阐明。 方法：对假手术和去卵巢（OVX）小鼠喂食含5%玉米油（CO）或5%鱼油（FO）的饲料。通过双能X线吸收法（DXA）分析骨矿物质密度。通过气相色谱法分析血清脂质谱。分别通过流式细胞术和酶联免疫吸附测定法（ELISA）分析活化T细胞中核因子κB受体活化因子配体（RANKL）的表达和细胞因子的产生。通过将骨髓（BM）细胞与1,25-二羟基维生素D3共同培养来生成破骨细胞。通过电泳迁移率变动分析测定BM巨噬细胞中NF-κB的活化情况。 结果与结论：喂食FO的小鼠血浆脂质C16:1n6、C20:5n3和C22:6n3显著增加，而C20:4n6和C18:2n6减少。喂食CO的OVX小鼠骨矿物质密度损失显著增加（左股骨远端为20%，腰椎为22.6%），而喂食FO的小鼠分别仅为10%且无变化。喂食CO的OVX小鼠活化CD4+T细胞中RANKL表达增加与骨矿物质密度损失相关，但喂食FO的小鼠无变化。与选定n-6脂肪酸（亚油酸[LA]和花生四烯酸[AA]）相比，体外添加选定的n-3脂肪酸（二十二碳六烯酸[DHA]和二十碳五烯酸[EPA]）可使BM细胞中抗酒石酸酸性磷酸酶（TRACP）活性和TRACP+多核细胞形成显著减少。DHA和EPA在体外也可抑制RANKL诱导的BM巨噬细胞NF-κB活化。假手术和OVX喂食FO小鼠的脾细胞培养基中肿瘤坏死因子-α（TNF-α）、白细胞介素（IL）-2和干扰素（IFN）-γ浓度均降低，假手术喂食FO小鼠的白细胞介素-6降低。总之，抑制破骨细胞生成和活化可能是膳食n-3脂肪酸减少OVX小鼠骨质流失的机制之一。
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