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骨关节炎(OA)患者外周血中金属蛋白酶(MMP - 3、MMP - 9)、核因子κB配体(RANKL)和一氧化氮(NO)的水平。

Levels of metalloproteinase (MMP-3, MMP-9), NF-kappaB ligand (RANKL), and nitric oxide (NO) in peripheral blood of osteoarthritis (OA) patients.

作者信息

Li Heng, Li Liqin, Min Jikang, Yang Honghang, Xu Xuchun, Yuan Yongjian, Wang Dan

机构信息

Department of Orthopaedics, Affiliated First People's Hospital of Huzhou Teachers College, Zhejiang Province, China, 313000.

出版信息

Clin Lab. 2012;58(7-8):755-62.

PMID:22997976
Abstract

BACKGROUND

The aim of this study was to judge whether there is a correlation between some biochemical features of knee osteoarthritic blood and clinical characteristics and to evaluate the potential relationship between osteoarthitis (OA) severity and putative biomarkers for the disease.

METHODS

105 patients suffering from knee OA were analyzed clinically (Lequesne's index) and radiographically (Kellgren and Lawrence, K&L). Plasma and peripheral blood mononuclear cells (PBMC) were harvested separately. Specimens were analyzed for concentrations of nitric oxide (NO), matrix metalloproteinase-3 (MMP-3), and matrix metalloproteinase-9 (MMP-9). Transcript levels of the receptor activator of NF-kB ligand (RANKL) mRNA, MMP-3mRNA, and MMP-9mRNA were measured using real-time quantitative RT-PCR.

RESULTS

Data certified significantly increasing concentrations of plasma MMP-3, MMP-9, and NO as well as transcript levels of RANKL mRNA and MMP-9 mRNA in early OA (at grade I). There was a positive correlation of MMP-3 and MMP-9 content in plasma and MMP-9 mRNA expression levels in PBMC with the severity of clinical symptoms (total Lequesne's scores) in early OA. NO content in plasma correlated with total Lequesne's scores, pain scores in response to pressure, and swelling scores of early OA patients (atgGrade I). Analogously, there were positive correlations of RANKL mRNA expression with total Lequesne's scores, pain scores in response to pressure, and swelling scores in OA patients at Grade I.

CONCLUSIONS

[corrected] Some biochemical factors, including content of NO, MMP-3, MMP-9, and transcript levels of some genes, including MMP-9 mRNA and RANKL mRNA, may be specific and sensitive enough to diagnose OA diseases at an early stage in the pathological process of OA when radiological features do not reflect degradation of articular cartilage. Therefore, proper regulation of these factors may be a promising and realistic new target for the treatment of degenerative osteoarticular diseases.

摘要

背景

本研究旨在判断膝骨关节炎血液的某些生化特征与临床特征之间是否存在相关性,并评估骨关节炎(OA)严重程度与该疾病假定生物标志物之间的潜在关系。

方法

对105例膝骨关节炎患者进行临床分析(使用Lequesne指数)和影像学分析(使用Kellgren和Lawrence,即K&L分级)。分别采集血浆和外周血单核细胞(PBMC)。分析样本中一氧化氮(NO)、基质金属蛋白酶-3(MMP-3)和基质金属蛋白酶-9(MMP-9)的浓度。使用实时定量逆转录聚合酶链反应(RT-PCR)测量核因子κB受体活化因子配体(RANKL)mRNA、MMP-3mRNA和MMP-9mRNA的转录水平。

结果

数据证实,在早期OA(I级)中,血浆MMP-3、MMP-9和NO的浓度以及RANKL mRNA和MMP-9 mRNA的转录水平显著升高。在早期OA中,血浆中MMP-3和MMP-9的含量以及PBMC中MMP-9 mRNA的表达水平与临床症状的严重程度(Lequesne总分)呈正相关。血浆中NO含量与早期OA患者(I级)的Lequesne总分、压痛评分和肿胀评分相关。类似地,在I级OA患者中,RANKL mRNA表达与Lequesne总分、压痛评分和肿胀评分呈正相关。

结论

一些生化因素,包括NO、MMP-3、MMP-9的含量以及一些基因的转录水平,如MMP-9 mRNA和RANKL mRNA,在OA病理过程中,当影像学特征未反映关节软骨退变时,可能具有足够的特异性和敏感性来早期诊断OA疾病。因此,对这些因素进行适当调控可能是治疗退行性骨关节疾病的一个有前景且现实的新靶点。

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