Migfilin's elimination from osteoarthritic chondrocytes further promotes the osteoarthritic phenotype via β-catenin upregulation

被引:9
作者
Gkretsi, Vasiliki [1 ]
Papanikolaou, Vassilis [1 ]
Dubos, Stephanie [1 ]
Papathanasiou, Ioanna [1 ,2 ]
Giotopoulou, Nikolina [1 ]
Valiakou, Vaia [1 ]
Wu, Chuanyue [3 ]
Malizos, Konstantinos N. [1 ,4 ]
Tsezou, Aspasia [1 ,2 ]
机构
[1] Ctr Res & Technol Thessaly CE RE TE TH, Dept Biomed Res & Technol, Larisa 41222, Greece
[2] Univ Thessaly, Fac Med, Dept Biol, Larisa 41110, Greece
[3] Univ Pittsburgh, Sch Med, Dept Pathol, Pittsburgh, PA 15261 USA
[4] Univ Thessaly, Fac Med, Dept Orthopaed, Larisa 41110, Greece
关键词
Osteoarthritis; Migfilin; beta-Catenin; Chondrocytes; Extracellular matrix; INTEGRIN-LINKED KINASE; HUMAN ARTICULAR-CARTILAGE; CELL-SHAPE MODULATION; PROTEOMIC CHARACTERIZATION; ACTIN CYTOSKELETON; FOCAL ADHESIONS; PROTEIN; EXPRESSION; ILK; ACTIVATION;
D O I
10.1016/j.bbrc.2012.12.008
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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 beta-catenin activation in OA chondrocytes, showing Migfilin to be inversely correlated with beta-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. (C) 2012 Elsevier Inc. All rights reserved.
引用
收藏
页码:494 / 499
页数:6
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