Differential proteome analysis of normal and osteoarthritic chondrocytes reveals distortion of vimentin network in osteoarthritis

Lambrecht, Stijn; Verbruggen, G.; Verdonk, Peter; Elewaut, Dirk; Deforce, Dieter

doi:10.1016/j.joca.2007.06.005

Cited by 76 publications

(68 citation statements)

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“…In contrast, disrupting the 19 actin microfilament network resulted in comparable cell deformations between shVim-20 hMSCs and shLacZ-hMSCs ( Figure 3B). Normalized aspect ratios were still slightly 21 higher for shVim-hMSCs compared to shLacZ-hMSCs, but no longer significant at both Recently, studies have found vimentin IFs to be disrupted in chondrocytes and even in 16 MSCs harvested from osteoarthritic bone marrow 4,16,27 . Because mechanical loading is without allowing for extended culture time, as previously described 33 .…”

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confidence: 93%

“…Mechanical properties and mechanotransduction are in 12 part regulated by the cytoskeleton, consisting primarily of actin microfilaments, 13 microtubules, and vimentin intermediate filaments (IFs) for cells of mesenchymal 14 lineage 5,7,19,23,24,29,30,34,36 . While their role in the pathogenesis of OA is still unknown, 15 vimentin IFs have recently been found to be disrupted or dispersed in osteoarthritic 16 chondrocytes 4,16 . Notably, vimentin has also been shown to be downregulated in MSCs 17 of osteoarthritic patients 27 , which raises questions about the potential efficacy of 18 autologous stem cell therapies for treatment of OA.…”

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confidence: 99%

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Deformability of Human Mesenchymal Stem Cells Is Dependent on Vimentin Intermediate Filaments

et al. 2017

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confidence: 93%

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confidence: 99%

Deformability of Human Mesenchymal Stem Cells Is Dependent on Vimentin Intermediate Filaments

et al. 2017

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“…The methodology developed for this investigation represents a considerable advancement on previous proteomic studies using in vitro systems to identify protein expression changes associated with cartilage pathology (6,7,20). This is the first differential proteomic analysis of cartilage-related samples using fluorescence DIGE to quantify protein expression differences.…”

Section: Discussionmentioning

confidence: 99%

“…Human chondrocyte and cartilage cultures have also been used to identify pathologic changes associated with osteoarthritis (OA), using proteomic tech-niques (6,7). However, the analysis of human tissue and synovial fluid is complicated by the genetic heterogeneity of patients, variation in disease stage, and the limited availability of well-matched control samples.…”

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confidence: 99%

Proteomic characterization of mouse cartilage degradation in vitro

Wilson¹,

Belluoccio²,

Little³

et al. 2008

Arthritis & Rheumatism

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Objective.To develop proteomics to analyze mouse cartilage degradation and correlate transcriptional and translational responses to catabolic stimuli.Methods. Proteomic techniques were used to analyze catabolism in mouse femoral head cartilage. Using specific methods to prepare cartilage extracts and conditioned media for 2-dimensional polyacrylamide gel electrophoresis and subsequent tandem mass spectrometry, we identified novel proteins and fragments released into the media of control, interleukin-1␣ (IL-1␣)-treated, and all-trans-retinoic acid (RetA)-treated explants. Fluorescence 2-dimensional difference gel electrophoresis was used to quantify protein expression changes. We also measured changes in messenger RNA (mRNA) expression to distinguish transcriptional and posttranslational regulation of released proteins.Results. Differentially abundant proteins in the media of control and treated explants included fragments of thrombospondin 1 and connective tissue growth factor. IL-1␣ stimulated release of the cartilage degeneration marker matrix metalloproteinase 3, as well as proteins with uncharacterized roles in cartilage pathology, such as neutrophil gelatinase-associated lipocalin. RetA stimulated release of the extracellular matrix proteins cartilage oligomeric matrix protein, link protein, and matrilin-3 into the media, which was accompanied by a dramatic reduction in the corresponding mRNA transcript levels. Gelsolin, which has been implicated in cytoskeletal reorganization in arthritis synovial fibroblasts but has not been previously associated with cartilage pathology, was regulated by IL-1␣ and RetA.Conclusion. In this first analysis of mouse cartilage degradation and protein release using proteomics, we identified proteins and fragments, some of which represent novel candidate biomarkers for cartilage degradation. Applying these proteomic techniques to wild-type and genetically modified mouse cartilage will provide insights into the mechanisms of cartilage degeneration.

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“…Subsequent validation experiments clearly pointed to distortion of the vimentin organization associated with OA. In addition, novel players were identified in processes known to be involved in OA pathogenesis, such as oxidative stress, apoptosis, and metabolic activation [70]. Undoubtedly, the results generated by such differential analyses will further contribute to our knowledge of processes activated in OA-chondrocytes.…”

Section: Cartilagementioning

confidence: 94%

Proteomics in rheumatology: The beginning of a fairy tale?

Lambrecht

Tilleman

Elewaut

et al. 2008

Proteomics Clinical Apps

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One of the major challenges in proteome research is to translate its applications to the setting of human diseases. Proteomics in rheumatology is an area with marked potential including applications ranging from diagnostics, over therapeutic monitoring to discovery of new potential therapeutic targets. Biomarkers will be essential to discriminate between clinical similar rheumatic diseases, to monitor disease-states or to install the best appropriate therapy. Especially in the field of rheumatology, analysis of specific genes and/or their expression products by pharmacogenetics/-genomics or pharmacoproteomics could be necessary to enable an effective, patient-tailored therapy. In rheumatology, direct examination of proteins may be of utmost importance, as it is already known that PTMs, such as citrullination of proteins or peptides, may be involved in certain rheumatic diseases. The discovery and validation of antibodies directed against citrullinated proteins/peptides in rheumatic diseases using proteome analysis approaches has been described. Gel-free methods, SELDI-approaches and classic 2-DE approaches have been deployed on body fluids as well as on target tissues in different rheumatic diseases. Proteomics in rheumatology is on the rise and pilot studies have indicated that the application of proteomicsbased technologies in rheumatic diseases appears to be an exciting example of translational research.

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Differential proteome analysis of normal and osteoarthritic chondrocytes reveals distortion of vimentin network in osteoarthritis

Abstract: All together, this study revealed substantial alterations in the vimentin cytoskeleton in OA-affected human articular chondrocytes.

Cited by 76 publications

References 41 publications

Deformability of Human Mesenchymal Stem Cells Is Dependent on Vimentin Intermediate Filaments

Deformability of Human Mesenchymal Stem Cells Is Dependent on Vimentin Intermediate Filaments

Proteomic characterization of mouse cartilage degradation in vitro

Proteomics in rheumatology: The beginning of a fairy tale?

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