Mechanical overload and chemical factors are both related to obesity-induced progression of knee osteoarthritis. The circadian rhythm is related to the development of metabolic syndrome and the progression of osteoarthritis, and the core clock genes nuclear receptor subfamily 1 group D member 1 (NR1D1) and brain and muscle arnt-like protein 1 (BMAL1) are dysregulated in cartilage from patients with osteoarthritis. Here, we focused on NR1D1 and investigated osteoarthritis-related changes and gene expression in a mouse model of diet-induced obesity. A high-fat diet was provided to C57BL6/J mice, and changes in body weight, blood lipids, and gene expression were investigated. Destabilization of the medial meniscus or sham surgery was performed on mice fed a high-fat diet or normal diet, and histological osteoarthritis-related changes and NR1D1 expression were investigated. The effects of the NR1D1 agonist SR9009 were also assessed. Mice fed a high-fat diet developed significant obesity and dyslipidemia. Nr1d1 and Bmal1 gene expression levels decreased in the liver and knee joints. Moreover, increased osteoarthritis progression and decreased NR1D1 protein expression were observed in high-fat diet-fed mice after surgical osteoarthritis induction. SR9009 decreased the progression of obesity, dyslipidemia, and osteoarthritis. Overall, obesity and dyslipidemia induced by the high-fat diet led to osteoarthritis progression and decreased NR1D1 expression. Thus, NR1D1 may play an important role in obesity-induced osteoarthritis.

中文翻译：

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肥胖诱导的骨关节炎进展病理学中的核受体亚家族 1 D 组成员 1

机械超负荷和化学因素都与肥胖引起的膝骨关节炎进展有关。昼夜节律与代谢综合征的发生和骨关节炎的进展有关，核心时钟基因核受体亚家族1组D成员1（NR1D1 ）和脑肌肉类蛋白1（BMAL1 ）) 在骨关节炎患者的软骨中失调。在这里，我们专注于 NR1D1，并在饮食诱导的肥胖小鼠模型中研究了骨关节炎相关的变化和基因表达。为 C57BL6/J 小鼠提供高脂肪饮食，并研究体重、血脂和基因表达的变化。对喂食高脂肪饮食或正常饮食的小鼠进行内侧半月板不稳定或假手术，并研究组织学骨关节炎相关变化和 NR1D1 表达。还评估了 NR1D1 激动剂 SR9009 的作用。喂食高脂肪饮食的小鼠出现明显的肥胖和血脂异常。Nr1d1和Bmal1肝脏和膝关节的基因表达水平下降。此外，在手术骨关节炎诱导后，在高脂肪饮食喂养的小鼠中观察到骨关节炎进展增加和 NR1D1 蛋白表达降低。SR9009 减缓了肥胖、血脂异常和骨关节炎的进展。总体而言，高脂肪饮食引起的肥胖和血脂异常导致骨关节炎进展并降低 NR1D1 表达。因此，NR1D1 可能在肥胖诱导的骨关节炎中发挥重要作用。