Objective

Obesity was once considered a risk factor for knee osteoarthritis (OA) primarily for biomechanical reasons. Here we provide an additional perspective by discussing how obesity also increases OA risk by altering metabolism and inflammation.

Design

This narrative review is presented in four sections: 1) metabolic syndrome and OA, 2) metabolic biomarkers of OA, 3) evidence for dysregulated chondrocyte metabolism in OA, and 4) metabolic inflammation: joint tissue mediators and mechanisms.

Results

Metabolic syndrome and its components are strongly associated with OA. However, evidence for a causal relationship is context dependent, varying by joint, gender, diagnostic criteria, and demographics, with additional environmental and genetic interactions yet to be fully defined. Importantly, some aspects of the etiology of obesity-induced OA appear to be distinct between men and women, especially regarding the role of adipose tissue. Metabolomic analyses of serum and synovial fluid have identified potential diagnostic biomarkers of knee OA and prognostic biomarkers of disease progression. Connecting these biomarkers to cellular pathophysiology will require future in vivo studies of joint tissue metabolism. Such studies will help reveal when a metabolic process or a metabolite itself is a causal factor in disease progression. Current evidence points towards impaired chondrocyte metabolic homeostasis and metabolic-immune dysregulation as likely factors connecting obesity to the increased risk of OA.

Conclusions

A deeper understanding of how obesity alters metabolic and inflammatory pathways in synovial joint tissues is expected to provide new therapeutic targets and an improved definition of “metabolic” and “obesity” OA phenotypes.

中文翻译：

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OA 基础知识。骨关节炎和软骨组织的一项倡议。 OA 中的肥胖和代谢因素

 客观的

主要出于生物力学原因，肥胖一度被认为是膝骨关节炎（OA）的危险因素。在这里，我们通过讨论肥胖如何通过改变新陈代谢和炎症来增加 OA 风险，从而提供了另一个视角。

 设计

本叙述性综述分为四个部分：1) 代谢综合征和 OA，2) OA 的代谢生物标志物，3) OA 中软骨细胞代谢失调的证据，4) 代谢炎症：关节组织介质和机制。

 结果

代谢综合征及其组成部分与 OA 密切相关。然而，因果关系的证据取决于具体情况，因关节、性别、诊断标准和人口统计数据而异，另外的环境和遗传相互作用尚未完全确定。重要的是，肥胖引起的 OA 病因学的某些方面在男性和女性之间似乎有所不同，特别是在脂肪组织的作用方面。血清和滑液的代谢组学分析已经确定了膝关节 OA 的潜在诊断生物标志物和疾病进展的预后生物标志物。将这些生物标志物与细胞病理生理学联系起来需要未来对关节组织代谢的体内研究。此类研究将有助于揭示代谢过程或代谢物本身何时是疾病进展的因果因素。目前的证据表明，软骨细胞代谢稳态受损和代谢免疫失调可能是导致肥胖与骨关节炎风险增加相关的因素。

 结论

更深入地了解肥胖如何改变滑膜关节组织的代谢和炎症途径，有望提供新的治疗靶点，并改进“代谢”和“肥胖”OA 表型的定义。