Institute of Ageing and Chronic Disease, William Henry Duncan Building, 6 West Derby Street, Liverpool L7 8TX, UK.
Centre for Proteome Research, Institute of Integrative Biology, Biosciences Building, Crown Street, University of Liverpool, Liverpool L69 7ZB, UK.
J Proteomics. 2019 Jun 30;202:103370. doi: 10.1016/j.jprot.2019.04.020. Epub 2019 Apr 25.
Articular conditions are common in horses and can result in loss of function, chronic pain and/or inability to work. Common conditions include osteoarthritis, osteochondrosis and synovial sepsis, which can be life-threatening, but despite the high clinical prevalence of these conditions, rapid and specific diagnosis, monitoring and prognostication remains a challenge for practicing veterinarians. Synovial fluid from a range of arthropathies was enriched for low abundance proteins using combinatorial peptide ligand ProteoMiner™ beads and analysed via liquid chromatography-tandem mass spectrometry. Changes in protein abundances were analysed using label-free quantification. Principle component analysis of differentially expressed proteins identified groupings associated with joint pathology. Findings were validated using ELISA. Lactotransferrin (LTF) abundance was increased in sepsis compared to all other groups and insulin-like growth factor-binding protein 6 (IGFBP6) abundance decreased in sepsis compared to other disease groups. Pathway analysis identified upregulation of the complement system in synovial joint sepsis and the downregulation of eukaryotic translation initiation factors and mTOR signalling pathways in both OA and OC compared to the healthy group. Overall, we have identified a catalogue of proteins which we propose to be involved in osteoarthritis, osteochondrosis and synovial sepsis pathogenesis. SIGNIFICANCE: Osteoarthritis, osteochondrosis and synovial sepsis, which can be life-threatening, are common articular conditions in which rapid and specific diagnosis, monitoring and prognostication remains a challenge for practicing veterinarians. This study has identified that the equine synovial fluid proteome exhibits distinctive profile changes between osteoarthritis, osteochondrosis, synovial sepsis and healthy joints. Elevated synovial abundance of lactotransferrin and decreased insulin-like growth factor-binding protein 6 were both found to distinguish synovial sepsis from all other study groups. Thus, these protein markers may have a future role in clinical practice to enable an earlier and reliable diagnosis of synovial sepsis.
关节疾病在马中很常见，可导致功能丧失、慢性疼痛和/或无法工作。常见疾病包括骨关节炎、骨软骨病和滑液脓毒症，这些疾病可能危及生命，但尽管这些疾病在临床上很常见，快速和特异性诊断、监测和预后仍然是执业兽医面临的挑战。使用组合肽配体 ProteoMiner™珠从各种关节病的滑液中富集低丰度蛋白质，并通过液相色谱-串联质谱法进行分析。使用无标记定量法分析蛋白质丰度的变化。差异表达蛋白的主成分分析确定了与关节病理相关的分组。使用 ELISA 验证发现。与所有其他组相比，脓毒症中乳转铁蛋白 (LTF) 的丰度增加，与其他疾病组相比，脓毒症中胰岛素样生长因子结合蛋白 6 (IGFBP6) 的丰度降低。途径分析表明，在滑膜关节脓毒症中补体系统上调，在 OA 和 OC 中与健康组相比，真核翻译起始因子和 mTOR 信号通路下调。总的来说，我们已经确定了一组我们认为参与骨关节炎、骨软骨病和滑液脓毒症发病机制的蛋白质。意义：骨关节炎、骨软骨病和滑液脓毒症可能危及生命，是马中常见的关节疾病，快速和特异性诊断、监测和预后仍然是执业兽医面临的挑战。这项研究表明，马的滑液蛋白质组在骨关节炎、骨软骨病、滑液脓毒症和健康关节之间表现出独特的变化特征。乳转铁蛋白的滑膜丰度升高和胰岛素样生长因子结合蛋白 6 的减少都被发现可将滑液脓毒症与所有其他研究组区分开来。因此，这些蛋白质标志物可能在未来的临床实践中有一定的作用，能够更早、更可靠地诊断滑液脓毒症。
