Objective OA is a very heterogeneous disease. Here, we aimed to differentiate OA patients based on their serum-induced cell-integrated signalling patterns. Design In order to monitor the activity of different cellular homeostasis-regulating pathways in response to patient serum, we analysed the response of human OA serum samples to 16 cell-based transcription factor luciferase reporter assays. In this study we compared serum samples from 55 patients with knee OA, 56 patients with hand OA and 42 healthy controls. Results Differential serum-induced pathway activity was observed between samples from healthy controls, knee OA and hand OA patients: serum of hand OA patients induced high MAPK-related AP1 activity whereas serum of knee OA patients induced more SRE, ISRE and SOX9 activity, which is related to ELK1-SRF, STAT1-STAT2 and SOX9 activity, respectively. Principal component analysis revealed that these differences differentiate hand OA from knee OA. Both hand and knee OA clustered clearly in two different endotypes each, but no principle component could be identified of these subtypes within either the hand OA or the knee OA sample group. Conclusion This study demonstrates that serum from hand OA and knee OA patients evokes diverse cellular signalling patterns that differentiates hand OA, knee OA and healthy controls. This underlines that the pathomolecular mechanisms of OA are likely significantly different between hand and knee OA, a finding that could lead to new insight into the pathobiology of OA endotypes and joint-specific therapies.

中文翻译：

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细胞整合血清诱导的信号传导模式可以区分手骨关节炎和膝关节骨关节炎患者


目的 OA 是一种异质性很强的疾病。在这里，我们旨在根据 OA 患者的血清诱导的细胞整合信号模式来区分他们。设计 为了监测不同细胞稳态调节途径对患者血清的响应活性，我们分析了人 OA 血清样品对 16 种基于细胞的转录因子荧光素酶报告基因测定的反应。在这项研究中，我们比较了 55 名膝关节 OA 患者、56 名手部 OA 患者和 42 名健康对照者的血清样本。结果 健康对照、膝关节 OA 和手部 OA 患者样本之间观察到血清诱导的途径活性差异：手部 OA 患者血清诱导较高的 MAPK 相关 AP1 活性，而膝关节 OA 患者血清诱导的 SRE 、 ISRE 和 SOX9 活性较高，分别与 ELK1-SRF 、 STAT1-STAT2 和 SOX9 活性相关。主成分分析显示，这些差异区分了手部 OA 和膝关节 OA。手部和膝关节 OA 均明显聚集在两种不同的内型中，但在手部 OA 或膝关节 OA 样本组中均未鉴定出这些亚型的主要成分。结论 本研究证明，手部 OA 和膝关节 OA 患者的血清会引起不同的细胞信号模式，从而区分手部 OA、膝关节 OA 和健康对照。这强调 OA 的病理分子机制在手部和膝关节 OA 之间可能显着不同，这一发现可能导致对 OA 内型和关节特异性治疗的病理生物学的新见解。