Aging and Metabolism Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK, 73104, USA.
Department of Biomedical Sciences, Ohio Musculoskeletal and Neurological Institute (OMNI), Ohio University, Athens, OH, 45701, USA.
Osteoarthritis Cartilage. 2022 Apr;30(4):501-515. doi: 10.1016/j.joca.2021.06.013. Epub 2021 Sep 17.
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.
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.
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.
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.
肥胖曾被认为是膝关节骨关节炎（OA）的一个风险因素，主要是基于生物力学原因。在这里，我们通过讨论肥胖如何通过改变代谢和炎症来增加 OA 风险，提供了另一个视角。
这篇叙述性综述分为四个部分：1）代谢综合征与 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。
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学因素而异，其环境和遗传相互作用仍有待充分定义。重要的是，肥胖引起的 OA 的病因学某些方面在男性和女性之间似乎存在差异，尤其是在脂肪组织的作用方面。对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，需要对关节组织代谢进行未来的体内研究。这些研究将有助于揭示代谢过程或代谢物本身是否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-免疫失调可能是肥胖与 OA 风险增加相关的因素。
更深入地了解肥胖如何改变滑膜关节组织中的代谢和炎症途径，有望为新的治疗靶点提供依据，并对“代谢性”和“肥胖性”OA 表型进行更好的定义。
