Glycation marker glucosepane increases with the progression of osteoarthritis and correlates with morphological and functional changes of cartilage in vivo.
Glycation marker glucosepane increases with the progression of osteoarthritis and correlates with morphological and functional changes of cartilage in vivo.
复制标题
DOI：
10.1186/s13075-018-1636-6
复制
发表时间：
2018-06-22
影响因子：
4.9
通讯作者：
Rabbani N
中科院分区：
文献类型：
--
作者：
Legrand C;Ahmed U;Anwar A;Rajpoot K;Pasha S;Lambert C;Davidson RK;Clark IM;Thornalley PJ;Henrotin Y;Rabbani N
最近发现，结合算法中的机器学习技术，改变血清糖化、氧化和硝化氨基酸以及羟脯氨酸和抗环瓜氨酸肽抗体状态，可以改善患者早期膝关节炎(包括骨关节炎)的诊断和分型。关节释放的糖化、氧化和硝化氨基酸与膝骨性关节炎的发生和进展的关系尚不清楚。我们在骨性关节炎动物模型和白细胞介素1β激活的体外人软骨细胞中研究了这一点，并将关键发现转译给骨性关节炎患者。对60只3周龄雄性Dunkin-Hartley豚鼠进行了研究。分别于4、12、20、28和36周龄处死12只动物，评估膝关节骨性关节炎的组织学严重程度，并评估软骨流变性。用白细胞介素1β处理多层培养的人软骨细胞10天。收集早期和晚期骨性关节炎患者和健康对照组，采集血样，制备血清或血浆。分析血清、血浆和培养液中的糖化、氧化和硝化氨基酸。随着年龄的增长，豚鼠骨性关节炎的严重程度逐渐增加。糖化氨基酸、氧化氨基酸和硝化氨基酸在36周时显著增加，葡萄糖苷和二氢酪氨酸分别从20周和28周开始递增。葡萄糖苷与骨性关节炎的严重程度呈正相关(r = 0.58，p <； 0.0001)和瞬时弹性系数(r = 0.52-0.56；p <； 0.0001)，无氧化加合物与骨性关节炎的严重程度呈正相关(p <； 0.0009-0.0062)，羟脯氨酸与软骨厚度呈正相关(p <； 0.0003-0.003)。IL-1β可促进体外培养的软骨细胞释放糖化和硝化氨基酸。在临床翻译中，与健康对照组相比，早期骨性关节炎患者(p <； 0.001)和晚期骨性关节炎患者(p <； 0.001)的血浆葡糖胺水平分别升高了38%和6倍。这些研究进一步推进了糖化、氧化和硝化氨基酸作为血清生物标记物在早期检测OA和其他关节炎疾病的诊断算法中的预期作用。据我们所知，在这里首次报道的血浆葡糖胺可以改善临床骨性关节炎的早期诊断和进展。本文的在线版本(10.1186/s13075-0181636-6)包含补充材料，授权用户可以使用。
Changes of serum concentrations of glycated, oxidized, and nitrated amino acids and hydroxyproline and anticyclic citrullinated peptide antibody status combined by machine learning techniques in algorithms have recently been found to provide improved diagnosis and typing of early-stage arthritis of the knee, including osteoarthritis (OA), in patients. The association of glycated, oxidized, and nitrated amino acids released from the joint with development and progression of knee OA is unknown. We studied this in an OA animal model as well as interleukin-1β-activated human chondrocytes in vitro and translated key findings to patients with OA. Sixty male 3-week-old Dunkin-Hartley guinea pigs were studied. Separate groups of 12 animals were killed at age 4, 12, 20, 28 and 36 weeks, and histological severity of knee OA was evaluated, and cartilage rheological properties were assessed. Human chondrocytes cultured in multilayers were treated for 10 days with interleukin-1β. Human patients with early and advanced OA and healthy controls were recruited, blood samples were collected, and serum or plasma was prepared. Serum, plasma, and culture medium were analyzed for glycated, oxidized, and nitrated amino acids. Severity of OA increased progressively in guinea pigs with age. Glycated, oxidized, and nitrated amino acids were increased markedly at week 36, with glucosepane and dityrosine increasing progressively from weeks 20 and 28, respectively. Glucosepane correlated positively with OA histological severity (r = 0.58, p < 0.0001) and instantaneous modulus (r = 0.52–0.56; p < 0.0001), oxidation free adducts correlated positively with OA severity (p < 0.0009–0.0062), and hydroxyproline correlated positively with cartilage thickness (p < 0.0003–0.003). Interleukin-1β increased the release of glycated and nitrated amino acids from chondrocytes in vitro. In clinical translation, plasma glucosepane was increased 38% in early-stage OA (p < 0.05) and sixfold in patients with advanced OA (p < 0.001) compared with healthy controls. These studies further advance the prospective role of glycated, oxidized, and nitrated amino acids as serum biomarkers in diagnostic algorithms for early-stage detection of OA and other arthritic disease. Plasma glucosepane, reported here for the first time to our knowledge, may improve early-stage diagnosis and progression of clinical OA. The online version of this article (10.1186/s13075-018-1636-6) contains supplementary material, which is available to authorized users.