In vitro osteoclast differentiation enhanced by hepatocyte supernatants from high-fat diet mice

IF 2.3 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY Biochemistry and Biophysics Reports Pub Date : 2024-07-13 DOI:10.1016/j.bbrep.2024.101788
Yan Wang , Fangli Zhou , Siyi Shu , Yunhong Wu , Haoming Tian , Yujue Li , Xiang Chen
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Abstract

Non-alcoholic fatty liver disease (NAFLD) is associated with abnormal bone metabolism, potentially mediated by elevated levels of proinflammatory cytokines such as tumor necrosis factor alpha (TNF-ɑ) and interleukin 6 (IL-6). This study aims to investigate the direct regulatory effects of liver tissues on osteoblast and osteoclast functions in vitro, focusing on the liver-bone axis in NAFLD. Twelve-week-old C57BL/6 mice were fed either a control diet or a high-fat diet (HFD) for 12 weeks. Bone structural parameters were assessed using microCT. Primary hepatocyte cultures were established from control and HFD-fed C57BL/6 mice, as well as IL-6−/− and TNF-α−/− mice. The supernatants from these hepatocyte cultures were used to induce differentiation in bone marrow cell-derived osteoblasts and osteoclasts in vitro. Results showed that mice on a HFD exhibited increased lipid infiltration in liver and bone marrow tissues, alongside reduced bone mass. Moreover, the supernatants from hepatocyte cultures from mice on a HFD displayed elevated TNF-α and IL-6 levels. These supernatants, particularly those derived from HFD-fed and IL-6−/− mice, significantly enhanced osteoclast differentiation in vitro. In contrast, supernatants from TNF-α−/− mice did not significantly affect osteoblast or osteoclast differentiation in vitro. In conclusions, this current study suggested that fatty liver tissues may negatively impact bone metabolism. Additionally, knockout of TNF-α and IL-6 genes revealed distinct influence on osteoblast and osteoclast functions, highlighting the complex interplay between live pathology and bone health.

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高脂饮食小鼠肝细胞上清液促进了体外破骨细胞分化
非酒精性脂肪肝(NAFLD)与骨代谢异常有关,可能由肿瘤坏死因子α(TNF-ɑ)和白细胞介素6(IL-6)等促炎细胞因子水平升高介导。本研究旨在体外研究肝组织对成骨细胞和破骨细胞功能的直接调节作用,重点研究非酒精性脂肪肝中的肝-骨轴。12周大的C57BL/6小鼠以对照组饮食或高脂饮食(HFD)喂养12周。使用显微CT评估骨骼结构参数。从对照组和喂食 HFD 的 C57BL/6 小鼠以及 IL-6-/- 和 TNF-α-/- 小鼠身上建立原代肝细胞培养物。这些肝细胞培养物的上清液用于体外诱导骨髓细胞衍生的成骨细胞和破骨细胞的分化。结果显示,高脂饮食小鼠的肝脏和骨髓组织中脂质浸润增加,同时骨量减少。此外,高脂饮食小鼠肝细胞培养物的上清液显示 TNF-α 和 IL-6 水平升高。这些上清液,尤其是那些来自高纤维脂肪喂养和IL-6-/-小鼠的上清液,在体外显著增强了破骨细胞的分化。相比之下,TNF-α-/-小鼠的上清液对体外成骨细胞或破骨细胞的分化没有明显影响。总之,本研究表明,脂肪肝组织可能会对骨代谢产生负面影响。此外,TNF-α和IL-6基因的敲除对成骨细胞和破骨细胞功能有不同的影响,突显了活体病理学与骨骼健康之间复杂的相互作用。
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来源期刊
Biochemistry and Biophysics Reports
Biochemistry and Biophysics Reports Biochemistry, Genetics and Molecular Biology-Biophysics
CiteScore
4.60
自引率
0.00%
发文量
191
审稿时长
59 days
期刊介绍: Open access, online only, peer-reviewed international journal in the Life Sciences, established in 2014 Biochemistry and Biophysics Reports (BB Reports) publishes original research in all aspects of Biochemistry, Biophysics and related areas like Molecular and Cell Biology. BB Reports welcomes solid though more preliminary, descriptive and small scale results if they have the potential to stimulate and/or contribute to future research, leading to new insights or hypothesis. Primary criteria for acceptance is that the work is original, scientifically and technically sound and provides valuable knowledge to life sciences research. We strongly believe all results deserve to be published and documented for the advancement of science. BB Reports specifically appreciates receiving reports on: Negative results, Replication studies, Reanalysis of previous datasets.
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