Conjugated linoleic Acid prevents ovariectomy-induced bone loss in mice by modulating both osteoclastogenesis and osteoblastogenesis.

Conjugated linoleic Acid prevents ovariectomy-induced bone loss in mice by modulating both osteoclastogenesis and osteoblastogenesis.
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DOI:
10.1007/s11745-013-3872-5
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发表时间:
2014-03
期刊:
影响因子:
1.9
通讯作者:
Williams, Paul
Williams, Paul
中科院分区:
医学4区
文献类型:
--
作者:
Rahman, Md Mizanur;Fernandes, Gabriel;Williams, Paul

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由于雌激素缺乏引起的绝经后骨质疏松症与严重的发病率和死亡率相关。共轭亚油酸(CLA)对小鼠、大鼠和人类骨密度(BMD)的有益作用已被报道,但长期补充CLA对卵巢切除诱导的小鼠骨丢失的作用及其机制尚未研究。8周龄卵巢切除(Ovx)和假手术的C57 BL/6小鼠喂养含0.5%红花油(SFO)或0.5%共轭亚油酸(CLA)的饲料24周,以检查BMD、骨转换标志物和骨生长因子。培养骨髓(BM)细胞以确定对炎症、破骨细胞生成和成骨细胞生成的影响。与SFO/Sham小鼠相比,SFO/OVX小鼠的股骨、胫骨和腰椎BMD显著降低;而CLA/OVX和CLA/Sham小鼠之间无差异。CLA抑制骨吸收标志物,而增强骨形成标志物在Ovx小鼠相比,SFO喂养的小鼠。RT-PCR和流式细胞仪分析结果显示,CLA抑制破骨细胞生成RANKL,刺激RANKL诱饵受体OPG的表达。CLA还抑制LPS刺激的脾细胞和骨髓细胞的促炎细胞因子和增强抗炎细胞因子的产生。此外,CLA抑制破骨细胞分化的BM和刺激骨髓基质细胞的成骨细胞分化的TRAP和茜素红染色,分别证实。总之,CLA不仅可以通过抑制雌激素缺乏引起的过度骨吸收,而且可以通过刺激新骨形成来预防绝经后骨质流失。CLA可能是治疗骨质疏松性骨丢失的一种潜在的替代疗法。
Postmenopausal osteoporosis due to estrogen deficiency is associated with severe morbidity and mortality. Beneficial effects of conjugated linoleic acid (CLA) on bone mineral density (BMD) have been reported in mice, rats and humans, but the effect of long term CLA supplementation against ovariectomy-induced bone loss in mice and the mechanisms underlying this effect have not been studied yet. Eight weeks old ovariectomized (Ovx) and sham operated C57BL/6 mice were fed either a diet containing 0.5% safflower oil (SFO) or 0.5% CLA for 24 weeks to examine BMD, bone turn over markers and osteotropic factors. Bone marrow (BM) cells were cultured to determine the effect on inflammation, osteoclastogenesis, and osteoblastogenesis. SFO/Ovx mice had significantly lower femoral, tibial and lumbar BMD compared to SFO/Sham mice; whereas, no difference was found between CLA/OVX and CLA/Sham mice. CLA inhibited bone resorption markers whereas enhanced bone formation markers in Ovx mice as compared to SFO fed mice. RT-PCR and FACS analyses of splenocytes revealed that CLA inhibited pro-osteoclastogenic RANKL and stimulated decoy receptor of RANKL, OPG expression. CLA also inhibited pro-inflammatory cytokine and enhanced anti-inflammatory cytokine production of LPS-stimulated splenocytes and bone marrow cells. Furthermore, CLA inhibited osteoclast differentiation in BM and stimulated osteoblast differentiation in BM stromal cells as confirmed by TRAP and Alizarin Red staining, respectively. In conclusion, CLA may prevent postmenopausal bone loss not only by inhibiting excessive bone resorption due to estrogen deficiency but also by stimulating new bone formation. CLA might be a potential alternative therapy against osteoporotic bone loss.
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期刊: LIPIDS
影响因子: 1.9
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期刊: Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research
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作者:
Barbour KE;Boudreau R;Danielson ME;Youk AO;Wactawski-Wende J;Greep NC;LaCroix AZ;Jackson RD;Wallace RB;Bauer DC;Allison MA;Cauley JA
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