Migfilin's elimination from osteoarthritic chondrocytes further promotes the osteoarthritic phenotype via β-catenin upregulation.
Migfilin's elimination from osteoarthritic chondrocytes further promotes the osteoarthritic phenotype via β-catenin upregulation.
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Migfilin从骨关节炎的软骨细胞中消除进一步通过β-catenin上调促进了骨关节炎的表型。
DOI：
10.1016/j.bbrc.2012.12.008
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发表时间：
2013-01-11
影响因子：
3.1
通讯作者：
Tsezou, Aspasia
中科院分区：
文献类型：
--
作者：
Gkretsi, Vasiliki;Papanikolaou, Vassilis;Dubos, Stephanie;Papathanasiou, Ioanna;Giotopoulou, Nikolina;Valiakou, Vaia;Wu, Chuanyue;Malizos, Konstantinos N.;Tsezou, Aspasia
骨关节炎（OA）是一种以软骨退化为特征的关节衰弱性疾病，但迄今为止，没有可用的药物治疗来抑制疾病进展，也没有任何可用的生物标志物来预测其发展。在本研究中，我们使用来自健康个体和OA患者的原代人关节软骨细胞，检测了新型细胞-ECM粘附相关分子如I整合素连接激酶（ILK）、PINCH、parvin、Mig-2和Migfilin在OA发病机制中的表达水平和可能参与。我们的研究结果表明，只有ILK和Migfilin上调OA相比，正常的软骨细胞。有趣的是，OA软骨细胞中的Migfilin沉默加重而不是改善骨关节炎表型，因为它导致甚至更高水平的分解代谢和肥大标志物，同时诱导ECM分子如聚集蛋白聚糖的减少。此外，我们还提供了OA软骨细胞中Migfilin和β-catenin激活之间的联系，表明Migfilin与β-catenin呈负相关。因此，本研究首次强调了Migfilin在OA中的作用，并强调了细胞-ECM粘附蛋白在OA发病机制中的重要性。
Osteoarthritis (OA) is a debilitating disease of the joints characterized by cartilage degradation but to date there is no available pharmacological treatment to inhibit disease progression neither is there any available biomarker to predict its development. In the present study, we examined the expression level and possible involvement of novel cell-ECM adhesion-related molecules such as Iintegrin Linked Kinase (ILK), PINCH, parvin, Mig-2 and Migfilin in OA pathogenesis using primary human articular chondrocytes from healthy individuals and OA patients. Our findings show that only ILK and Migfilin were upregulated in OA compared to the normal chondrocytes. Interestingly, Migfilin silencing in OA chondrocytes rather exacerbated than ameliorated the osteoarthritic phenotype, as it resulted in even higher levels of catabolic and hypertrophic markers while at the same time induced reduction in ECM molecules such as aggrecan. Furthermore, we also provide a link between Migfilin and β-catenin activation in OA chondrocytes, showing Migfilin to be inversely correlated with β-catenin. Thus, the present study emphasizes for the first time to our knowledge the role of Migfilin in OA and highlights the importance of cell-ECM adhesion proteins in OA pathogenesis.
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影响因子：
4.9
作者：
Felson DT
通讯作者：
Felson DT
影响因子：
--
作者：
Lawrence, Reva C.;Felson, David T.;Wolfe, Frederick
通讯作者：
Wolfe, Frederick
影响因子：
4.2
作者：
Guo, Dunming;Tan, Wenfeng;Zhang, Zhongnan
通讯作者：
Zhang, Zhongnan
DOI：
10.1073/pnas.060579697
发表时间：
2000-03-28
影响因子：
11.1
作者：
Persad, S;Attwell, S;Dedhar, S
通讯作者：
Dedhar, S
影响因子：
2.8
作者：
Papathanasiou, Ioanna;Malizos, Konstantinos N.;Tsezou, Aspasia
通讯作者：
Tsezou, Aspasia