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骨关节炎患者和实验性关节炎模型中抑瘤素 M 表达与炎症表型的关系。

Association between Oncostatin M Expression and Inflammatory Phenotype in Experimental Arthritis Models and Osteoarthritis Patients.

机构信息

Department of Orthopedics, University Medical Centre Utrecht, 3584 CX Utrecht, The Netherlands.

Department of Oral and Maxillofacial Surgery & Special Dental Care, University Medical Center Utrecht, 3584 CX Utrecht, The Netherlands.

出版信息

Cells. 2021 Feb 27;10(3):508. doi: 10.3390/cells10030508.

Abstract

Pro-inflammatory cytokines are considered to play a major role in osteoarthritis (OA), yet so far, the specific cytokines involved in the pathology of OA have not been identified. Oncostatin M (OSM) is a cytokine from the interleukin 6 (IL-6) family that has been shown to be elevated in synovial fluid of most rheumatoid arthritis (RA) patients, but only in a limited subset of OA patients. Little is known about OSM in the different joint tissues during OA and how its expression correlates with hallmarks of disease. Here, we mapped OSM expression in the joint tissues of two rat models of arthritis: an acute inflammatory model and an instability-induced osteoarthritic model. OSM expression was correlated with hallmarks of OA, namely cartilage damage, synovitis, and osteophyte formation. Reanalysis of an existing dataset on cytokine profiling of OA synovial fluid was performed to assess pattern differences between patients positive and negative for OSM. In the inflammatory model, OSM expression correlated with synovitis and osteophyte formation but not with cartilage damage. On the contrary, in the instability model of OA, an increase in synovitis, cartilage damage, and osteophyte formation was observed without changes in OSM expression. In line with these findings, synovial fluid of OA patients with detectable OSM contained higher levels of other inflammatory cytokines, namely interferon gamma (IFN-γ), IL-1α and tumor necrosis factor alpha (TNF-α), likely indicating a more inflammatory state. Taken together these data indicate OSM might play a prominent role in inflammatory phenotypes of OA.

摘要

促炎细胞因子被认为在骨关节炎 (OA) 中起主要作用,但到目前为止,OA 病理涉及的特定细胞因子尚未确定。肿瘤坏死因子 M (OSM) 是白细胞介素 6 (IL-6) 家族的一种细胞因子,已被证明在大多数类风湿关节炎 (RA) 患者的滑液中升高,但仅在有限的 OA 患者亚组中升高。关于 OA 不同关节组织中的 OSM 及其表达与疾病特征的相关性知之甚少。在这里,我们在两种关节炎大鼠模型的关节组织中绘制了 OSM 表达图谱:一种急性炎症模型和一种不稳定诱导的骨关节炎模型。OSM 表达与 OA 的特征标志物相关,即软骨损伤、滑膜炎和骨赘形成。对 OA 滑液细胞因子谱的现有数据集进行了重新分析,以评估 OSM 阳性和阴性患者之间的模式差异。在炎症模型中,OSM 表达与滑膜炎和骨赘形成相关,但与软骨损伤无关。相反,在 OA 的不稳定模型中,观察到滑膜炎、软骨损伤和骨赘形成增加,而 OSM 表达没有变化。与这些发现一致的是,可检测到 OSM 的 OA 患者的滑液中含有更高水平的其他炎症细胞因子,即干扰素 γ (IFN-γ)、IL-1α 和肿瘤坏死因子 α (TNF-α),可能表明炎症状态更严重。综上所述,这些数据表明 OSM 可能在 OA 的炎症表型中起重要作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5532/7997294/608a09955db3/cells-10-00508-g001.jpg

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