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Quantitative proteomics reveals regulatory differences in the chondrocyte secretome from human medial and lateral femoral condyles in osteoarthritic patients

机译:定量蛋白质组学揭示了骨关节炎患者人内侧和外侧股骨les软骨细胞分泌组的调节差异

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Background 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. Results 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. Conclusions 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.
机译:背景技术骨关节炎(OA)是一种破坏性关节疾病,目前尚无已知的生物标志物可用于早期诊断。为了鉴定潜在的疾病生物标志物并进一步了解OA的疾病机理,我们将SILAC定量蛋白质组学应用于OA膝软骨细胞的分泌液组中,称为高Mankin(HM)评分分泌液组。定量比较了同一膝关节内侧和外侧股骨con突软骨细胞的分泌,因为内侧股骨con通常比外侧con受OA影响更大,这已通过Mankin评分得到证实。内侧/外侧比较也来自软骨细胞的分泌液组,该分泌液组取自一个没有临床明显关节疾病的个体,称为低Mankin(LM)评分分泌液组。结果我们在HM分泌组中鉴定出825种蛋白质,其中69种在比较内侧和外侧股室时显示差异表达。 LM评分的股骨dy表现出通过Mankin评分评估的内侧隔室OA的早期迹象。我们在这里报告了OA疾病机制(例如OA)的几种感兴趣的蛋白质的鉴定和相对定量。 CYTL1,DMD和STAB1以及可能的早期疾病标志物,例如TIMP1,PPP2CA和B2M。结论本研究揭示了OA患者中内侧/外侧股骨con之间的蛋白质丰度差异。这些法规上的差异扩展了有关OA疾病标记和机制的知识。

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