PDF(Pubmed)
Abstract：
Knee osteoarthritis (KOA) is characterized by low-grade inflammation, loss of articular cartilage, subchondral bone remodeling, synovitis, osteophyte formation, and pain. Strong, continuous pain may indicate the need for joint replacement in patients with end-stage OA, although postoperative pain (POP) of at least a two-month duration persists in 10-40% of patients with OA.
OBJECTIVE: The inflammation observed in joint tissues is linked to pain caused by the production of proinflammatory cytokines. Since the biosynthesis of cytokines requires energy, their production is supported by extensive metabolic conversions of carbohydrates and fatty acids, which could lead to a disruption in cellular homeostasis. Therefore, this study aimed to investigate the association between POP development and disturbances in energy metabolic conversions, focusing on carbohydrate and fatty acid metabolism.
METHODS: Peripheral blood samples were collected from 26 healthy subjects and 50 patients with end-stage OA before joint replacement surgery. All implants were validated by orthopedic surgeons, and patients with OA demonstrated no inherent abnormalities to cause pain from other reasons than OA disease, such as malalignment, aseptic loosening, or excessive bleeding. Pain levels were assessed before surgery using the visual analogue scale (VAS) and neuropathic pain questionnaires, DN4 and PainDETECT. Functional activity was evaluated using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). Three and six months after surgery, pain indices according to a VAS of 30 mm or higher were considered. Total RNA isolated from whole blood was analyzed using quantitative real-time RT-PCR (qRT-PCR) for the expression of genes related to carbohydrate and fatty acid metabolism. Protein levels of the examined genes were measured using an ELISA in the peripheral blood mononuclear cells (PBMCs). We used qRT-PCR because it is the most sensitive and reliable method for gene expression analysis, while an ELISA was used to confirm our qRT-PCR results.
RESULTS: Among the study cohort, 17 patients who reported POP demonstrated significantly higher (p < 0.05) expressions of the genes PKM2, LDH, SDH, UCP2, CPT1A, and ACLY compared to pain-free patients with KOA. Receiver-operating characteristic (ROC) curve analyses confirmed the association between these gene expressions and pain development post-arthroplasty. A principle component analysis identified the prognostic values of ACLY, CPT1A, AMPK, SDHB, Caspase 3, and IL-1β gene expressions for POP development in the examined subjects.
CONCLUSIONS: These findings suggest that the disturbances in energy metabolism, as observed in the PBMCs of patients with end-stage KOA before arthroplasty, may contribute to POP development. An understanding of these metabolic processes could provide insights into the pathogenesis of KOA. Additionally, our findings can be used in a clinical setting to predict POP development in end-stage patients with KOA before arthroplasty.
OBJECTIVE: The inflammation observed in joint tissues is linked to pain caused by the production of proinflammatory cytokines. Since the biosynthesis of cytokines requires energy, their production is supported by extensive metabolic conversions of carbohydrates and fatty acids, which could lead to a disruption in cellular homeostasis. Therefore, this study aimed to investigate the association between POP development and disturbances in energy metabolic conversions, focusing on carbohydrate and fatty acid metabolism.
METHODS: Peripheral blood samples were collected from 26 healthy subjects and 50 patients with end-stage OA before joint replacement surgery. All implants were validated by orthopedic surgeons, and patients with OA demonstrated no inherent abnormalities to cause pain from other reasons than OA disease, such as malalignment, aseptic loosening, or excessive bleeding. Pain levels were assessed before surgery using the visual analogue scale (VAS) and neuropathic pain questionnaires, DN4 and PainDETECT. Functional activity was evaluated using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). Three and six months after surgery, pain indices according to a VAS of 30 mm or higher were considered. Total RNA isolated from whole blood was analyzed using quantitative real-time RT-PCR (qRT-PCR) for the expression of genes related to carbohydrate and fatty acid metabolism. Protein levels of the examined genes were measured using an ELISA in the peripheral blood mononuclear cells (PBMCs). We used qRT-PCR because it is the most sensitive and reliable method for gene expression analysis, while an ELISA was used to confirm our qRT-PCR results.
RESULTS: Among the study cohort, 17 patients who reported POP demonstrated significantly higher (p < 0.05) expressions of the genes PKM2, LDH, SDH, UCP2, CPT1A, and ACLY compared to pain-free patients with KOA. Receiver-operating characteristic (ROC) curve analyses confirmed the association between these gene expressions and pain development post-arthroplasty. A principle component analysis identified the prognostic values of ACLY, CPT1A, AMPK, SDHB, Caspase 3, and IL-1β gene expressions for POP development in the examined subjects.
CONCLUSIONS: These findings suggest that the disturbances in energy metabolism, as observed in the PBMCs of patients with end-stage KOA before arthroplasty, may contribute to POP development. An understanding of these metabolic processes could provide insights into the pathogenesis of KOA. Additionally, our findings can be used in a clinical setting to predict POP development in end-stage patients with KOA before arthroplasty.
摘要：
膝关节骨性关节炎(KOA)以低度炎症为特征,关节软骨丢失，软骨下骨重建，滑膜炎,骨赘形成,和痛苦。坚强,持续疼痛可能表明终末期OA患者需要进行关节置换，尽管10-40％的OA患者持续至少两个月的术后疼痛（POP）。
目的：在关节组织中观察到的炎症与由促炎细胞因子产生引起的疼痛有关。由于细胞因子的生物合成需要能量，它们的生产得到碳水化合物和脂肪酸广泛代谢转化的支持，这可能导致细胞稳态的破坏。因此,本研究旨在探讨POP发育与能量代谢转化紊乱之间的关系，专注于碳水化合物和脂肪酸代谢。
方法：在关节置换手术前采集26名健康受试者和50名终末期OA患者的外周血。所有植入物都经过整形外科医生的验证，和OA患者没有表现出固有的异常引起疼痛的原因，而不是OA疾病，比如不对准，无菌性松动,或者出血过多.术前使用视觉模拟评分(VAS)和神经性疼痛问卷评估疼痛水平,DN4和油漆检测。使用西安大略省和麦克马斯特大学骨关节炎指数（WOMAC）评估功能活性。手术后三个月和六个月，根据30mm或更高的VAS考虑疼痛指数.对于与碳水化合物和脂肪酸代谢相关的基因的表达,使用定量实时RT-PCR(qRT-PCR)分析从全血中分离的总RNA。使用ELISA在外周血单核细胞(PBMC)中测量所检查基因的蛋白质水平。我们使用qRT-PCR，因为它是基因表达分析最敏感和可靠的方法，而ELISA用于确认我们的qRT-PCR结果。
结果：在研究队列中，17例报告POP的患者表现出明显较高（p<0.05）的基因PKM2，LDH的表达，SDH,UCP2,CPT1A,与无痛KOA患者相比。受试者工作特征（ROC）曲线分析证实了这些基因表达与关节置换术后疼痛发展之间的关联。主成分分析确定了ACLY的预后价值，CPT1A,AMPK,SDHB,Caspase3和IL-1β基因表达用于被检查受试者中的POP发育。
结论：这些发现表明，能量代谢紊乱，如在关节置换术前终末期KOA患者的PBMC中观察到的，可能有助于POP的发展。对这些代谢过程的理解可以提供对KOA发病机理的见解。此外,我们的研究结果可用于临床预测关节置换术前KOA终末期患者POP的发生.
目的：在关节组织中观察到的炎症与由促炎细胞因子产生引起的疼痛有关。由于细胞因子的生物合成需要能量，它们的生产得到碳水化合物和脂肪酸广泛代谢转化的支持，这可能导致细胞稳态的破坏。因此,本研究旨在探讨POP发育与能量代谢转化紊乱之间的关系，专注于碳水化合物和脂肪酸代谢。
方法：在关节置换手术前采集26名健康受试者和50名终末期OA患者的外周血。所有植入物都经过整形外科医生的验证，和OA患者没有表现出固有的异常引起疼痛的原因，而不是OA疾病，比如不对准，无菌性松动,或者出血过多.术前使用视觉模拟评分(VAS)和神经性疼痛问卷评估疼痛水平,DN4和油漆检测。使用西安大略省和麦克马斯特大学骨关节炎指数（WOMAC）评估功能活性。手术后三个月和六个月，根据30mm或更高的VAS考虑疼痛指数.对于与碳水化合物和脂肪酸代谢相关的基因的表达,使用定量实时RT-PCR(qRT-PCR)分析从全血中分离的总RNA。使用ELISA在外周血单核细胞(PBMC)中测量所检查基因的蛋白质水平。我们使用qRT-PCR，因为它是基因表达分析最敏感和可靠的方法，而ELISA用于确认我们的qRT-PCR结果。
结果：在研究队列中，17例报告POP的患者表现出明显较高（p<0.05）的基因PKM2，LDH的表达，SDH,UCP2,CPT1A,与无痛KOA患者相比。受试者工作特征（ROC）曲线分析证实了这些基因表达与关节置换术后疼痛发展之间的关联。主成分分析确定了ACLY的预后价值，CPT1A,AMPK,SDHB,Caspase3和IL-1β基因表达用于被检查受试者中的POP发育。
结论：这些发现表明，能量代谢紊乱，如在关节置换术前终末期KOA患者的PBMC中观察到的，可能有助于POP的发展。对这些代谢过程的理解可以提供对KOA发病机理的见解。此外,我们的研究结果可用于临床预测关节置换术前KOA终末期患者POP的发生.
