亚油酸阻碍早期成骨细胞分化并损害体外氧化磷酸化

IF 3
Paula-Dene C. Nesbeth , Thomas R. Ziegler , Ashish Kumar Tripathi , Sadaf Dabeer , Daiana Weiss , Li Hao , Matthew R. Smith , Dean P. Jones , Kristal M. Maner-Smith , Chia-Ling Tu , Wenhan Chang , M. Neale Weitzmann , Jessica A. Alvarez
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引用次数: 0

摘要

背景亚油酸(LNA)是一种必需的多不饱和脂肪酸(PUFA),在细胞功能中发挥着至关重要的作用。然而,摄入过量的 LNA(西方饮食的特点)会对细胞和器官产生有害影响。人体观察研究表明,血浆中 LNA 的浓度与骨矿物质密度之间存在反比关系。方法使用小鼠骨髓基质细胞(BMSC)和 MC3T3-E1 成骨细胞前体研究 LNA 对成骨细胞分化、细胞生物能和体外氧化 PUFA 代谢产物产生的影响。结果 LNA处理可降低碱性磷酸酶活性(成骨细胞分化的早期标志物),但对已形成的成骨细胞或已分化的成骨细胞的矿化没有影响。LNA 通过抑制参与成骨细胞分化的关键转录因子 Runx2 和 Osterix 以及参与骨形成的其他关键成骨细胞相关因子的表达来抑制成骨细胞的承诺。结论我们的研究结果表明,LNA 抑制了成骨细胞的早期分化,这种抑制作用与氧化的 PUFA 代谢产物的产生增加有关,而氧化的 PUFA 代谢产物可能会损害通过氧化磷酸化产生的能量。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Linoleic acid blunts early osteoblast differentiation and impairs oxidative phosphorylation in vitro

Background

Linoleic acid (LNA), an essential polyunsaturated fatty acid (PUFA), plays a crucial role in cellular functions. However, excessive intake of LNA, characteristic of Western diets, can have detrimental effects on cells and organs. Human observational studies have shown an inverse relationship between plasma LNA concentrations and bone mineral density. The mechanism by which LNA impairs the skeleton is unclear, and there is a paucity of research on the effects of LNA on bone-forming osteoblasts.

Methods

The effect of LNA on osteoblast differentiation, cellular bioenergetics, and production of oxidized PUFA metabolites in vitro, was studied using primary mouse bone marrow stromal cells (BMSC) and MC3T3-E1 osteoblast precursors.

Results

LNA treatment decreased alkaline phosphatase activity, an early marker of osteoblast differentiation, but had no effect on committed osteoblasts or on mineralization by differentiated osteoblasts. LNA suppressed osteoblast commitment by blunting the expression of Runx2 and Osterix, key transcription factors involved in osteoblast differentiation, and other key osteoblast-related factors involved in bone formation. LNA treatment was associated with increased production of oxidized LNA- and arachidonic acid-derived metabolites and blunted oxidative phosphorylation, resulting in decreased ATP production.

Conclusion

Our results show that LNA inhibited early differentiation of osteoblasts and this inhibitory effect was associated with increased production of oxidized PUFA metabolites that likely impaired energy production via oxidative phosphorylation.

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来源期刊
Prostaglandins, leukotrienes, and essential fatty acids
Prostaglandins, leukotrienes, and essential fatty acids Clinical Biochemistry, Endocrinology, Diabetes and Metabolism
CiteScore
5.30
自引率
0.00%
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0
审稿时长
64 days
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