Low-Density Lipoprotein Receptor-Related Protein 5 (LRP5) Expression in Human Osteoarthritic Chondrocytes
Low-Density Lipoprotein Receptor-Related Protein 5 (LRP5) Expression in Human Osteoarthritic Chondrocytes
复制标题
DOI：
10.1002/jor.20993
复制
发表时间：
2010-03-01
影响因子：
2.8
通讯作者：
Tsezou, Aspasia
中科院分区：
文献类型：
--
作者：
Papathanasiou, Ioanna;Malizos, Konstantinos N.;Tsezou, Aspasia
本研究的目的是研究骨关节炎中Wnt/β-连环蛋白通路的激活以及低密度脂蛋白受体相关蛋白5（LRP 5）在人骨关节炎软骨细胞中的作用。还评估了1，25（OH）（2）D-3对人软骨细胞中LRP 5基因表达的影响。从11名接受全膝关节置换手术的原发性骨关节炎（OA）患者获得人软骨。从5名健康个体获得正常软骨。使用实时PCR研究β-连环蛋白和LRP 5 mRNA水平，使用Western印迹分析研究LRP 5蛋白表达。此外，我们评估了1，25（OH）（2）D-3对骨关节炎软骨细胞中LRP 5 mRNA表达水平的影响。使用针对LRP 5的小干扰RNA（siRNA）阻断LRP 5表达，随后分别通过real-Lime PCR和Western印迹分析评估MMP-13 mRNA和蛋白水平。我们证实了OA中Wnt/β-连环蛋白通路的激活，因为我们观察到骨关节炎软骨细胞中β-连环蛋白mRNA表达的显著上调。我们还观察到，与正常软骨相比，骨关节炎软骨中LRP 5 mRNA和蛋白表达显著上调，维生素D进一步增加了LRP 5 mRNA表达。使用针对LRP 5的siRNA阻断LRP 5表达导致MMP-13 mRNA和蛋白质表达的显著降低我们的发现表明LRP 5的分解代谢作用在人骨关节炎中由Wnt/β-连环蛋白途径介导（C）2009骨科研究学会出版，Wiley Periodicals，Inc J Orthop Res 28 348-353，2010
The aim of this study was to investigate the activation of the Wnt/beta-catenin pathway in osteoarthritis and the role of low-density lipoprotein receptor-related protein 5 (LRP5) in human osteoarthritic chondrocytes. The influence of 1,25(OH)(2)D-3 on the expression of the LRP5 gene in human chondrocytes was also assessed Human cartilage was obtained from 11 patients with primary osteoarthritis (OA) undergoing total knee replacement surgery Normal cartilage was obtained from five healthy individuals Beta-catenin and LRP5 mRNA levels were investigated using real-time PCR and LRP5 protein expression using Western blot analysis. Furthermore, we evaluated the effect of 1,25(OH)(2)D-3 on LRP5 mRNA expression levels in osteoarthritic chondrocytes Blocking LRP5 expression was performed using small interfering RNA (siRNA) against LRP5, and Subsequent MMP-13 mRNA and protein levels were evaluated by real-Lime PCR and Western blot analysis, respectively. We confirmed the activation of the Wnt/beta-catenin pathway in OA, as we observed significant up-regulation of beta-catenin mRNA expression in osteoarthritic chondrocytes We also observed that LRP5 mRNA and protein expression were significantly up-regulated in osteoarthritic cartilage compared to normal cartilage, and LRP5 mRNA expression was further increased by vitamin D Also, blocking LRP5 expression using siRNA against LRP5 resulted in a significant decrease in MMP-13 mRNA and protein expressions Our findings suggest the catabolic role of LRP5 is mediated by the Wnt/beta-catenin pathway in human osteoarthritis (C) 2009 Orthopaedic Research Society Published by Wiley Periodicals, Inc J Orthop Res 28 348-353, 2010