肝损伤的严重程度决定了骨的恶化:MASLD和骨关节炎之间有一个共同的病理生理轴
Mercedes Del Rio-Moreno1,2, Sher Bahadur Poudel3, Lukas Stilgenbauer4
1Section of Endocrinology, Diabetes, and Metabolism, Department of Medicine, University of Illinois at Chicago, Chicago, IL, USA.
GeroScience
|July 27, 2025
概括
在小鼠中,代谢功能障碍相关的脂肪肝炎 (MASH) 导致骨和关节的恶化,包括骨质疏松症和骨关节炎. 这项研究揭示了一个共同的途径,将肝损伤与骨问题联系起来,这表明了结合治疗的潜力.
科学领域:
- 肝病学 肝病学是一种肝病学.
- 整形外科 整形外科 整形外科
- 代谢疾病 代谢疾病
背景情况:
- 非酒精性脂肪肝 (NAFLD) 和代谢综合征 (MetS) 与骨质疏松症和关节炎 (OA) 等骨和关节疾病有关.
- 代谢功能障碍相关的脂肪酸性肝病 (MASLD) 包括从简单脂肪酸到脂肪酸性肝炎 (MASH) 的情况,可能有纤维化.
- 这些疾病的患病率与年龄一起增加.
研究的目的:
- 调查代谢综合征中肝损伤对骨恶化的贡献.
- 建立代谢功能障碍相关的脂肪肝炎 (MASH) 和骨/关节病理之间的机制联系.
主要方法:
- 雄性小鼠被食高脂肪,高胆固醇和高果糖 (HFCF) 饮食以诱导MASH和纤维化.
- 对照小鼠接受了与营养相匹配的低脂肪,胆固醇和果糖 (LFCF) 饮食.
- 骨完整性被评估使用小CT的股骨和膝盖关节分析.
- 膝盖组织中的基因表达通过散装RNA测序来分析.
主要成果:
- 患有MASH和纤维化的小鼠表现出显著的皮质稀薄,缩小了轨道的厚度,以及股骨中较低的骨矿物质密度.
- 膝关节表现出亚冠骨损失,中枢软骨侵蚀,以及因诺斯,NLRP3和β-银酸酶的冠状细胞表达增加.
- 大量RNA-seq在膝盖组织中确定了与干扰素相关的和应激反应的上调的途径和下调的细胞外矩阵组织途径.
结论:
- 在MASH中肝损伤的严重程度与骨和关节完整性的恶化之间存在机械联系.
- 这些发现表明,MASLD和骨关节炎之间有一个共同的病理生理轴.
- 这凸显了针对炎症或肝脂代谢的治疗方法在同时治疗这两种疾病的潜力.
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