Matrix metalloproteinase protein expression profiles cannot distinguish between normal and early osteoarthritic synovial fluid.
Matrix metalloproteinase protein expression profiles cannot distinguish between normal and early osteoarthritic synovial fluid.
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DOI：
10.1186/1471-2474-13-126
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发表时间：
2012-07-23
影响因子：
2.3
通讯作者：
Krawetz R
中科院分区：
文献类型：
--
作者：
Heard BJ;Martin L;Rattner JB;Frank CB;Hart DA;Krawetz R
骨关节炎（OA）和风湿性关节炎（RA）是导致关节表面关节软骨退化的疾病。基质金属蛋白酶（MMP）是一种酶，有助于包括软骨在内的全身组织的自然重塑。然而，一些MMPs与OA和RA的进展有关，因为它们的表达水平和激活状态可以随着疾病的发作而显著改变。然而，它仍然是未知的，如果正常和关节炎关节表现出独特的MMP表达谱，如果是这样，MMP表达谱可以用来识别早期OA患者。在这项研究中，在高度表征的正常膝关节和临床诊断为OA（早期和晚期）或RA的膝关节中检查了MMPs 1、2、3、7、8、9、12和13以及MMPs的组织抑制剂（TIMPs）1、2、3和4的滑液蛋白表达水平。本研究的目的是确定正常、OA和RA患者是否表现出独特的MMP亚组表达谱，以及早期OA患者是否具有独特的MMP表达谱，该表达谱可用作早期诊断标志物。从严格表征的正常膝关节和诊断为OA（早期和晚期）或RA的关节中抽吸滑液。采用多重技术定量12例早期OA患者、17例诊断为晚期OA患者、15例RA患者和25例正常膝关节滑液中8种MMPs和4种TIMPs的蛋白表达水平。主成分分析（PCA）被用来揭示MMPs是最有影响力的治疗组之间的区别。使用K均值聚类来验证通过PCA对受试者的视觉分组。在正常和关节炎滑液之间观察到MMPs和TIMPs的表达水平的显着差异（MMP 12除外）。PCA证明MMPs 2、8和9可用于有效地将诊断患有晚期关节炎的个体与早期骨关节炎和正常个体分开，然而，这些MMP谱不能将早期OA与正常滑液分开。通过PCA还发现了晚期OA和RA受试者之间的明显分离。K-均值聚类验证了3个聚类的存在：与早期OA聚类的正常关节，以及晚期OA或RA的单独聚类。这项研究表明，独特的MMP和TIMP的表达谱存在于正常的，先进的OA和RA滑液。这些MMP谱可用于区分晚期OA和RA滑液与早期OA和正常滑液，甚至区分来自OA和RA关节的滑液样品。虽然这种方法不能用于早期OA的诊断，但滑液中MMP和TIMP的高通量多重技术可证明可用于确定疾病状态的严重程度和/或量化个体对疾病干预的反应。
Osteoarthritis (OA) and Rheumatoid arthritis (RA) are diseases which result in the degeneration of the joint surface articular cartilage. Matrix Metalloproteinases (MMPs) are enzymes that aid in the natural remodelling of tissues throughout the body including cartilage. However, some MMPs have been implicated in the progression of OA and RA as their expression levels and activation states can change dramatically with the onset of disease. Yet, it remains unknown if normal and arthritic joints demonstrate unique MMPs expression profiles, and if so, can the MMP expression profile be used to identify patients with early OA. In this study, the synovial fluid protein expression levels for MMPs 1, 2, 3, 7, 8, 9, 12 & 13, as well as those for the Tissue Inhibitors of MMPs (TIMPs) 1, 2, 3, & 4 were examined in highly characterized normal knee joints, and knee joints with clinically diagnosed OA (early and advanced) or RA. The purpose of this study was to determine if normal, OA, and RA patients exhibit unique expression profiles for a sub-set of MMPs, and if early OA patients have a unique MMP expression profile that could be used as an early diagnostic marker. Synovial fluid was aspirated from stringently characterized normal knee joints, and in joints diagnosed with either OA (early and advanced) or RA. Multiplexing technology was employed to quantify protein expression levels for 8 MMPs and 4 TIMPs in the synovial fluid of 12 patients with early OA, 17 patients diagnosed with advanced OA, 15 with RA and 25 normal knee joints. Principle component analysis (PCA) was used to reveal which MMPs were most influential in the distinction between treatment groups. K – means clustering was used to verify the visual grouping of subjects via PCA. Significant differences in the expression levels of MMPs and TIMPs were observed between normal and arthritic synovial fluids (with the exception of MMP 12). PCA demonstrated that MMPs 2, 8 & 9 can be used to effectively separate individuals diagnosed with advanced arthritis from early osteoarthritic and normal individuals, however, these MMP profiles do not separate early OA from normal synovial fluid. An apparent separation between advanced OA and RA subjects was also revealed through PCA. K-means clustering verified the presence of 3 clusters: normal joints clustered with early OA, and separate clusters of advanced OA or RA. This study demonstrates that unique MMP and TIMP expression profiles are present within normal, advanced OA and RA synovial fluid. These MMP profiles can be used to distinguish advanced OA & RA synovial fluid from early OA & normal synovial fluid, and even between synovial fluid samples from OA and RA joints. Although this methodology cannot be used for the diagnosis of early OA, high throughput multiplex technology of MMPs and TIMPs in synovial fluid may prove useful in determining the severity of the disease state, and/or quantifying the response of individuals to disease interventions.
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