Proteomic analysis of synovial fluid from the osteoarthritic knee: comparison with transcriptome analyses of joint tissues.
Proteomic analysis of synovial fluid from the osteoarthritic knee: comparison with transcriptome analyses of joint tissues.
复制标题
DOI：
10.1002/art.37823
复制
发表时间：
2013-04
影响因子：
--
通讯作者：
Aliprantis, Antonios O.
中科院分区：
文献类型：
--
作者：
Ritter, Susan Y.;Subbaiah, Roopashree;Bebek, Gurkan;Crish, James;Scanzello, Carla R.;Krastins, Bryan;Sarracino, David;Lopez, Mary F.;Crow, Mary K.;Aigner, Thomas;Goldring, Mary B.;Goldring, Steven R.;Lee, David M.;Gobezie, Reuben;Aliprantis, Antonios O.
最常见的关节疾病——骨关节炎（OA）的病理生理学仍然知之甚少。由于滑液 (SF) 沐浴在关节软骨和滑膜中，因此我们推断，对其在健康和 OA 中的蛋白质成分进行比较分析可以识别与关节损伤有关的途径。对 OA 患者和对照受试者的膝关节 SF 进行蛋白质组学分析，并与来自软骨和滑膜的微阵列表达数据进行比较。使用二维微分凝胶电泳 (2D-DIGE) 和质谱 (MS) 对来自对照受试者以及早期和晚期 OA 患者（每组 n=10）的年龄匹配的膝关节 SF 样本进行比较。使用多重肽选择反应监测 (SRM) 检测的 MS 来确认独立 OA 患者队列中蛋白质子集的差异表达。通过 Ingenuity 通路分析对蛋白质组结果进行分析，并与已发表的滑膜组织和软骨 mRNA 谱进行比较。 66 种蛋白质在健康和 OA SF 中存在差异。在这些蛋白质中确定了三个主要途径：急性期反应、补体和凝血途径。通过SRM测定证实了5种蛋白的差异表达。对差异存在的蛋白质对应的转录本的集中分析表明，滑膜和软骨组织都可能对 OA SF 蛋白质组有贡献。参与急性期反应、补体和凝血途径的蛋白质在 OA 患者的 SF 中受到差异性调节，表明它们会导致关节损伤。有必要验证这些途径及其作为 OA 生物标志物或治疗靶点的效用。
The pathophysiology of the most common joint disease, osteoarthritis (OA), remains poorly understood. Since synovial fluid (SF) bathes joint cartilage and synovium, we reasoned that a comparative analysis of its protein constituents in health and OA could identify pathways involved in joint damage. A proteomic analysis of knee SF from OA patients and control subjects was performed and compared to microarray expression data from cartilage and synovium. Age-matched knee SF samples from control subjects, and patients with early- and late-stage OA (n=10 per group) were compared using two-dimensional differential gel electrophoresis (2D-DIGE) and mass spectrometry (MS). A MS with multiplexed peptide selected reaction monitoring (SRM) assay was used to confirm differential expression of a subset of proteins in an independent OA patient cohort. Proteomic results were analyzed by Ingenuity pathway analysis and compared to published synovial tissue and cartilage mRNA profiles. 66 proteins were differentially present in healthy and OA SF. Three major pathways were identified among these proteins: the acute phase response, and the complement and coagulation pathways. Differential expression of 5 proteins was confirmed by SRM assay. A focused analysis of transcripts corresponding to the differentially present proteins indicates that both synovial and cartilage tissues may contribute to the OA SF proteome. Proteins involved in the acute phase response, complement and coagulation pathways are differentially regulated in SF of OA patients suggesting they contribute to joint damage. Validation of these pathways and their utility as biomarkers or therapeutic targets in OA is warranted.
登录
查看更多内容
影响因子：
4.4
作者：
Kamphorst, Jurre J.;van der Heijden, Rob;Hankemeier, Thomas
通讯作者：
Hankemeier, Thomas
影响因子：
9.9
作者：
Lange, Vinzenz;Picotti, Paola;Domon, Bruno;Aebersold, Ruedi
通讯作者：
Aebersold, Ruedi
影响因子：
7
作者：
Pearle, A. D.;Scanzello, C. R.;Crow, M. K.
通讯作者：
Crow, M. K.
影响因子：
46.9
作者：
Addona, Terri A.;Shi, Xu;Keshishian, Hasmik;Mani, D. R.;Burgess, Michael;Gillette, Michael A.;Clauser, Karl R.;Shen, Dongxiao;Lewis, Gregory D.;Farrell, Laurie A.;Fifer, Michael A.;Sabatine, Marc S.;Gerszten, Robert E.;Carr, Steven A.
通讯作者：
Carr, Steven A.
影响因子：
3.3
作者：
Mateos, Jesus;Lourido, Lucia;Blanco, Francisco J.
通讯作者：
Blanco, Francisco J.