Ex-Vivo Equine Cartilage Explant Osteoarthritis Model - A Metabolomics and Proteomics Study
Ex-Vivo Equine Cartilage Explant Osteoarthritis Model - A Metabolomics and Proteomics Study
复制标题
离体马软骨外植体骨关节炎模型 - 代谢组学和蛋白质组学研究
DOI：
10.1101/2020.03.03.974501
复制
发表时间：
2020
期刊：
影响因子：
--
通讯作者：
Anderson J
中科院分区：
文献类型：
--
作者：
Anderson J
骨关节炎是一种与年龄相关的退行性肌肉骨骼疾病，其特征是关节软骨丧失、滑膜炎和软骨下骨硬化。骨关节炎的发病机制尚未完全阐明，临床上尚无骨关节炎特异性生物标志物。离体马软骨外植体（n = 5）在肿瘤坏死因子-α（TNF-α）/白细胞介素-1β（IL-1β）补充培养基中孵育8天，在第2、5和8天除去并更换培养基。对所有时间点的 8 天软骨外植体和培养基样品的乙腈代谢物提取物进行一维 (1D)1H 核磁共振代谢组分析，并对培养基样品进行质谱蛋白质组分析。在软骨内，TNF-α/IL-1β 治疗后葡萄糖和赖氨酸升高，而腺苷、丙氨酸、甜菜碱、肌酸、肌醇和尿苷降低。在培养基中，分别在 1-2、3-5 和 6-8 天鉴定出 4、4 和 6 个差异丰富的代谢物以及 154、138 和 72 个差异丰富的蛋白质，包括治疗后丙氨酸减少和异亮氨酸、烯醇化酶 1、波形蛋白和核纤层蛋白 A/C 增加。九种潜在的新型骨关节炎新肽在处理过的培养基中升高。涉及的途径主要是那些参与细胞运动的途径。我们的创新研究提供了有关早期骨关节炎发病机制的深入信息，使临床标志物和可能的新治疗靶点具有潜在的转化。
Osteoarthritis is an age-related degenerative musculoskeletal disease characterized by loss of articular cartilage, synovitis, and subchondral bone sclerosis. Osteoarthritis pathogenesis is yet to be fully elucidated with no osteoarthritis-specific biomarkers in clinical use.Ex vivoequine cartilage explants (n= 5) were incubated in tumor necrosis factor-α (TNF-α)/interleukin-1β (IL-1β)-supplemented culture media for 8 days, with the media removed and replaced at 2, 5, and 8 days. Acetonitrile metabolite extractions of 8 day cartilage explants and media samples at all time points underwent one-dimensional (1D)1H nuclear magnetic resonance metabolomic analysis, with media samples also undergoing mass spectrometry proteomic analysis. Within the cartilage, glucose and lysine were elevated following TNF-α/IL-1β treatment, while adenosine, alanine, betaine, creatine, myo-inositol, and uridine decreased. Within the culture media, 4, 4, and 6 differentially abundant metabolites and 154, 138, and 72 differentially abundant proteins were identified at 1–2, 3–5, and 6–8 days, respectively, including reduced alanine and increased isoleucine, enolase 1, vimentin, and lamin A/C following treatment. Nine potential novel osteoarthritis neopeptides were elevated in the treated media. Implicated pathways were dominated by those involved in cellular movement. Our innovative study has provided insightful information on early osteoarthritis pathogenesis, enabling potential translation for clinical markers and possible new therapeutic targets.
登录
查看更多内容
DOI：
10.1016/j.pnmrs.2017.01.001
发表时间：
2017-05
影响因子：
6.1
作者：
Marshall DD;Powers R
通讯作者：
Powers R
影响因子：
2.6
作者：
Bertuglia A;Pagliara E;Grego E;Ricci A;Brkljaca-Bottegaro N
通讯作者：
Brkljaca-Bottegaro N
马腕关节软骨纤连蛋白分布与训练、关节位置和软骨退化相关。
影响因子：
2.2
作者：
R. Murray;H. C. Janicke;F. Henson;A. Goodship
通讯作者：
A. Goodship
影响因子：
2.8
作者：
Damyanovich, AZ;Staples, JR;Marshall, KW
通讯作者：
Marshall, KW
影响因子：
4.9
作者：
Peffers MJ;Cillero-Pastor B;Eijkel GB;Clegg PD;Heeren RM
通讯作者：
Heeren RM