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α-Linolenic Acid Inhibits RANKL-Induced Osteoclastogenesis In Vitro and Prevents Inflammation In Vivo

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机构: [1]West China School of Public Health, West China Fourth Hospital, Sichuan University, Chengdu 610041, China. [2]Department of Healthcare-Associated Infection Management, The Affiliated Hospital of Guizhou Medical University, Guiyang 550004, China. [3]Department of Laboratory Medicine, Chengdu Second People's Hospital, Chengdu 610041, China. [4]Food Safety Monitoring and Risk Assessment Key Laboratory of Sichuan Province, Department of Public Health Laboratory Sciences, West China School of Public Health, Sichuan University, Chengdu 610041, China. [5]Non-Communicable Diseases Research Center, West China-PUMC C. C. Chen Institute of Health, Sichuan University, Chengdu 610041, China.
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关键词: alpha-linolenic acid osteoclastogenesis anti-inflammation ovariectomized rat Zanthoxylum bungeanum seed oil

摘要:
Inflammation is an important risk factor for bone-destroying diseases. Our preliminary research found that Zanthoxylum bungeanum seed oil (ZBSO) is abundant in unsaturated fatty acids and could inhibit osteoclastogenesis in receptor activator of nuclear factor κB ligand (RANKL)-induced RAW264.7 cells. However, the key constituents in ZBSO in the prevention of osteoclastogenesis and its possible mechanism related to inflammation are still unclear. Therefore, in this study, oleic acid (OA), linoleic acid (LA), palmitoleic acid (PLA), and alpha-linolenic acid (ALA) in ZBSO, havingthe strongest effect on RANKL-induced osteoclastogenesis, were selected by a tartrate-resistant acid phosphatase (TRAP) staining method. Furthermore, the effects of the selected fatty acids on anti-inflammation and anti-osteoclastogenesis in vitro and in vivo were assessed using RT-qPCR. Among the four major unsaturated fatty acids we tested, ALA displayed the strongest inhibitory effect on osteoclastogenesis. The increased expression of free fatty acid receptor 4 (FFAR4) and β-arrestin2 (βarr2), as well as the decreased expression of nuclear factor-kappa B (NF-κB), tumor necrosis factor-α (TNF-α), nuclear factor of activated T-cells c1 (NFATc1), and tartrate-resistant acid phosphatase (TRAP) in RAW264.7 cells after ALA treatment were observed. Moreover, in ovariectomized osteoporotic rats with ALA preventive intervention, we found that the expression of TNF-α, interleukin-6 (IL-6), interleukin-1β (IL-1β), NFATc1, and TRAP were decreased, while with the ALA therapeutic intervention, downregulated expression of NF-κB, NFATc1, TRAP, and transforming growth factor beta-activated kinase 1 (TAK1) were noticed. These results indicate that ALA, as the major unsaturated fatty acid in ZBSO, could inhibit RANKL-induced osteoclastogenesis via the FFAR4/βarr2 signaling pathway and could prevent inflammation, suggesting that ZBSO may be a promising potential natural product of unsaturated fatty acids and a dietary supplement for the prevention of osteoclastogenesis and inflammatory diseases.

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出版当年[2023]版:
大类 | 2 区 农林科学
小类 | 2 区 食品科技
最新[2023]版:
大类 | 2 区 农林科学
小类 | 2 区 食品科技
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第一作者机构: [1]West China School of Public Health, West China Fourth Hospital, Sichuan University, Chengdu 610041, China.
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通讯机构: [1]West China School of Public Health, West China Fourth Hospital, Sichuan University, Chengdu 610041, China. [4]Food Safety Monitoring and Risk Assessment Key Laboratory of Sichuan Province, Department of Public Health Laboratory Sciences, West China School of Public Health, Sichuan University, Chengdu 610041, China. [5]Non-Communicable Diseases Research Center, West China-PUMC C. C. Chen Institute of Health, Sichuan University, Chengdu 610041, China.
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