title: Migfilin's elimination from osteoarthritic chondrocytes further promotes the osteoarthritic phenotype via β-catenin upregulation.
abstract: 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.
authors.affiliation: Center for Research and Technology-Thessaly (CE.RE.TE.TH), Department of Biomedical Research and Technology, Larissa 41222, Greece. vasso.gkretsi@gmail.com
authors.forename: Vasiliki
authors.initials: V
authors.lastname: Gkretsi
authors.forename: Vassilis
authors.initials: V
authors.lastname: Papanikolaou
authors.forename: Stephanie
authors.initials: S
authors.lastname: Dubos
authors.forename: Ioanna
authors.initials: I
authors.lastname: Papathanasiou
authors.forename: Nikolina
authors.initials: N
authors.lastname: Giotopoulou
authors.forename: Vaia
authors.initials: V
authors.lastname: Valiakou
authors.forename: Chuanyue
authors.initials: C
authors.lastname: Wu
authors.forename: Konstantinos N
authors.initials: KN
authors.lastname: Malizos
authors.forename: Aspasia
authors.initials: A
authors.lastname: Tsezou
mesh_terms: D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D019902:Chondrocytes / Q000378:metabolism* / Q000473:pathology; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000378:metabolism*; D018450:Disease Progression; D005109:Extracellular Matrix / Q000378:metabolism; D020868:Gene Silencing; D006801:Humans; D053509:Matrix Metalloproteinase 13 / Q000096:biosynthesis / Q000235:genetics; D010003:Osteoarthritis / Q000378:metabolism* / Q000473:pathology; D010641:Phenotype; D012333:RNA, Messenger / Q000096:biosynthesis; D015854:Up-Regulation; D051176:beta Catenin / Q000096:biosynthesis*
chemical_list: D015815:Cell Adhesion Molecules; D003598:Cytoskeletal Proteins; C473794:FBLIM1 protein, human; D012333:RNA, Messenger; D051176:beta Catenin; C507079:MMP13 protein, human; D053509:Matrix Metalloproteinase 13