Global metabolic profiling of human osteoarthritic synovium.
Global metabolic profiling of human osteoarthritic synovium.
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DOI：
10.1016/j.joca.2011.10.010
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发表时间：
2012-01
影响因子：
7
通讯作者：
Nettles, D. L.
中科院分区：
文献类型：
--
作者：
Adams, S. B., Jr.;Setton, L. A.;Kensicki, E.;Bolognesi, M. P.;Toth, A. P.;Nettles, D. L.
骨关节炎(OA)是一种与身体许多腹泻关节的疼痛和功能丧失有关的衰弱疾病。对骨性关节炎严重程度和/或进展的评估通常基于放射学分期和疼痛程度，这并不总是与疾病的严重程度或关节功能障碍相关，可能会被其他因素混淆1。最近，人们对确定OA1的生化特征感兴趣，该特征可在血清、尿液和/或滑液中检测到，代表可重复和可预测的OA发病和/或进展的生物标志物。这项研究的目的是使用全球代谢谱来确定培养的人类滑膜组织的不同代谢谱，这些组织来自终末期骨性关节炎患者，与很少或没有疾病证据的患者相比。虽然培养组织的代谢图谱预计不会在体内图谱中再现，但预计终末期疾病引起的新陈代谢扰动将导致体外代谢图谱与很少或没有疾病证据的组织的代谢图谱不同。由于代谢组的扰动通常发生在基因组或蛋白质组改变之前，代谢组学分析可能为OA的发生和/或进展提供一个改变的生化图谱的早期窗口，并可能提供一组独特的潜在药物靶点。滑膜是有针对性的，因为它被认为是疾病进展的中介物；骨关节炎滑膜已被证明表达促炎细胞因子，如肿瘤坏死因子-α(肿瘤坏死因子-α)、白介素1-β(IL-1β)和IL-62，提示病变的滑膜衬里可以产生一套理想的生物标志物来诊断和/或监测疾病的进展。取自病变关节(早期或晚期骨性关节炎)的滑膜外植体培养上清液，利用基于液相色谱(LC)和气相色谱(GC)/质谱仪(MS)的技术平台进行全球代谢谱分析。通过将实验样品中的离子特征与新陈代谢公司(北卡罗来纳州达勒姆)开发的化学标准条目参考库进行自动比较来鉴定代谢物。全球代谢图谱在所有样本组中鉴定出105种不同的化合物，其中11种化合物在终末期和非疾病/早期疾病组之间显示出显著不同的相对浓度。胶原代谢、支链氨基酸代谢、能量代谢和色氨酸代谢的代谢产物是最重要的化合物，表明随着疾病的进展，代谢状态发生了变化。
Osteoarthritis (OA) is a debilitating disease associated with pain and loss of function in numerous diarthrodial joints of the body. Assessments of the severity and/or progression of OA are commonly based on radiographic stages and pain level, which aren’t always correlated to severity of disease or joint dysfunction and may be confounded by other factors1. There has been recent interest in identifying a biochemical signature of OA1that may be detected in serum, urine, and/or synovial fluid that would represent repeatable and predictable biomarkers of OA onset and/or progression. The objective of this study was to use global metabolic profiling to identify a distinct metabolic profile for cultured human synovial tissue from patients with end-stage OA compared to patients with little or no evidence of disease. While metabolic profiles from cultured tissues are not expected to reproduce in vivo profiles, it is expected that perturbations in metabolism caused by end-stage disease would result in differences in metabolic profiles in vitro compared to tissue with little or no evidence of disease. Because metabolomic perturbations often occur prior to alterations in the genome or proteome, metabolomic analysis possibly provides an earlier window to an altered biochemical profile for OA onset and/or progression, and may provide a unique set of potential drug targets. The synovium was targeted because it has been implicated in OA as a mediator of disease progression; osteoarthritic synovium has been demonstrated to express pro-inflammatory cytokines, such as Tumor Necrosis Factor - α (TNF-α), Interleukin-1 β (IL-1β), and IL-62, suggesting that a diseased synovial lining could produce an ideal set of biomarkers for diagnosing OA and/or monitoring disease progression. Media from the culture of synovial explants dissected from diseased human joints (early or end-stage OA) was subjected to global metabolic profiling with a liquid chromatography (LC)/and gas chromatography (GC)/mass spectrophotometry (MS)-based technology platform. Metabolites were identified by automated comparison of the ion features in the experimental samples to a reference library of chemical standard entries developed at Metabolon, Inc (Durham, NC). Global metabolic profiling resulted in the identification of 105 distinct compounds across all sample groups, with 11 compounds showing significantly different relative concentrations between end-stage and no/early disease groups. Metabolites specific to collagen metabolism, branched-chain amino acid metabolism, energy metabolism and tryptophan metabolism were amongst the most significant compounds, suggesting an altered metabolic state with disease progression.
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影响因子：
2.8
作者：
Damyanovich, AZ;Staples, JR;Marshall, KW
通讯作者：
Marshall, KW
影响因子：
7
作者：
Lamers, RJAN;van Nesselrooij, JHJ;DeGroot, J
通讯作者：
DeGroot, J
影响因子：
6.8
作者：
Husek, Petr;Svagera, Zdenek;Simek, Petr
通讯作者：
Simek, Petr
DOI：
10.1074/mcp.m800292-mcp200
发表时间：
2009-01
期刊：
Molecular & cellular proteomics : MCP
影响因子：
--
作者：
Ruiz-Romero C;Calamia V;Mateos J;Carreira V;Martínez-Gomariz M;Fernández M;Blanco FJ
通讯作者：
Blanco FJ
影响因子：
6.1
作者：
Shigemura, Yasutaka;Iwai, Koji;Sato, Kenji
通讯作者：
Sato, Kenji