Department of Clinical Chemistry and Transfusion Medicine, Institute of Biomedicine, Sahlgrenska Academy at the Sahlgrenska University Hospital, University of Gothenburg, Gothenburg, Sweden.
Department of Biomedical Sciences and Veterinary Public Health, Division of Pathology, Pharmacology and Toxicology, Box 7028, SLUS-75007 Uppsala, Sweden.
Proteome Sci. 2013 Oct 4;11(1):43. doi: 10.1186/1477-5956-11-43.
Osteoarthritis (OA) is a destructive joint disease and there are no known biomarkers available for an early diagnosis. To identify potential disease biomarkers and gain further insight into the disease mechanisms of OA we applied quantitative proteomics with SILAC technology on the secretomes from chondrocytes of OA knees, designated as high Mankin (HM) scored secretome. A quantitative comparison was made between the secretomes of the medial and lateral femur condyle chondrocytes in the same knee since the medial femur condyle is usually more affected in OA than the lateral condyle, which was confirmed by Mankin scoring. The medial/lateral comparison was also made on the secretomes from chondrocytes taken from one individual with no clinically apparent joint-disease, designated as low Mankin (LM) scored secretome.
We identified 825 proteins in the HM secretome and 69 of these showed differential expression when comparing the medial and lateral femoral compartment. The LM scored femoral condyle showed early signs of OA in the medial compartment as assessed by Mankin score. We here report the identification and relative quantification of several proteins of interest for the OA disease mechanism e.g. CYTL1, DMD and STAB1 together with putative early disease markers e.g. TIMP1, PPP2CA and B2M.
The present study reveals differences in protein abundance between medial/lateral femur condyles in OA patients. These regulatory differences expand the knowledge regarding OA disease markers and mechanisms.
骨关节炎(OA)是一种破坏性关节疾病,目前尚无可用的早期诊断生物标志物。为了鉴定潜在的疾病生物标志物并深入了解 OA 的疾病机制,我们应用 SILAC 技术的定量蛋白质组学对 OA 膝关节软骨细胞的分泌组进行了研究,命名为高 Mankin(HM)评分的分泌组。对同一膝关节中内侧和外侧股骨髁软骨细胞的分泌组进行了定量比较,因为 OA 通常更影响内侧股骨髁,这通过 Mankin 评分得到了证实。对来自无临床明显关节疾病的个体的软骨细胞的分泌组也进行了内侧/外侧比较,命名为低 Mankin(LM)评分的分泌组。
我们在 HM 分泌组中鉴定了 825 种蛋白质,其中 69 种在比较内侧和外侧股骨间室时表现出差异表达。LM 评分的股骨髁内侧间室通过 Mankin 评分显示出 OA 的早期迹象。我们在此报告了几种与 OA 疾病机制相关的感兴趣蛋白的鉴定和相对定量,例如 CYTL1、DMD 和 STAB1,以及潜在的早期疾病标志物,例如 TIMP1、PPP2CA 和 B2M。
本研究揭示了 OA 患者内侧/外侧股骨髁之间蛋白质丰度的差异。这些调节差异扩展了我们对 OA 疾病标志物和机制的认识。