Grupo de Investigación en Reumatología, Instituto de Investigación Biomédica de A Coruña (INIBIC), Agrupación estratégica CICA-INIBIC, Complexo Hospitalario Universitario de A Coruña (CHUAC), Sergas. Universidade da Coruña (UDC), 15006 A Coruña, Spain.
Section for Pharmacology and Pharmaceutical Biosciences, Department of Pharmacy, University of Oslo, 0363 Oslo, Norway.
Cells. 2020 Mar 27;9(4):809. doi: 10.3390/cells9040809.
Osteoarthritis (OA) is the most frequent joint disease; however, the etiopathogenesis is still unclear. Chondrocytes rely primarily on glycolysis to meet cellular energy demand, but studies implicate impaired mitochondrial function in OA pathogenesis. The relationship between mitochondrial dysfunction and OA has been established. The aim of the study was to examine the differences in glucose and Fatty Acids (FA) metabolism, especially with regards to metabolic flexibility, in cybrids from healthy (N) or OA donors. Glucose and FA metabolism were studied using D-[C(U)]glucose and [1-C]oleic acid, respectively. There were no differences in glucose metabolism among the cybrids. Osteoarthritis cybrids had lower acid-soluble metabolites, reflecting incomplete FA β-oxidation but higher incorporation of oleic acid into triacylglycerol. Co-incubation with glucose and oleic acid showed that N but not OA cybrids increased their glucose metabolism. When treating with the mitochondrial inhibitor etomoxir, N cybrids still maintained higher glucose oxidation. Furthermore, OA cybrids had higher oxidative stress response. Combined, this indicated that N cybrids had higher metabolic flexibility than OA cybrids. Healthy donors maintained the glycolytic phenotype, whereas OA donors showed a preference towards oleic acid metabolism. Interestingly, the results indicated that cybrids from OA patients had mitochondrial impairments and reduced metabolic flexibility compared to N cybrids.
骨关节炎（OA）是最常见的关节疾病；然而，其病因仍然不清楚。软骨细胞主要依赖糖酵解来满足细胞的能量需求，但研究表明，线粒体功能障碍与 OA 的发病机制有关。已经确定了线粒体功能障碍与 OA 之间的关系。本研究旨在研究来自健康（N）或 OA 供体的细胞杂种中葡萄糖和脂肪酸（FA）代谢的差异，特别是代谢灵活性。使用 D-[C（U）]葡萄糖和[1-C]油酸分别研究葡萄糖和 FA 代谢。细胞杂种之间的葡萄糖代谢没有差异。OA 细胞杂种的酸溶性代谢物较低，反映出 FA β-氧化不完全，但油酸掺入三酰甘油的量较高。与葡萄糖和油酸共孵育表明，N 细胞杂种而非 OA 细胞杂种增加了葡萄糖代谢。当用线粒体抑制剂 etomoxir 处理时，N 细胞杂种仍保持较高的葡萄糖氧化。此外，OA 细胞杂种的氧化应激反应更高。综上所述，这表明 N 细胞杂种比 OA 细胞杂种具有更高的代谢灵活性。健康供体保持糖酵解表型，而 OA 供体则表现出对油酸代谢的偏好。有趣的是，结果表明与 N 细胞杂种相比，来自 OA 患者的细胞杂种存在线粒体损伤和代谢灵活性降低。
