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Perturbation of adhesion molecule-mediated chondrocyte-matrix interactions by 4-hydroxynonenal binding: implication in osteoarthritis pathogenesis

Rana El-Bikai, Mélanie Welman, Yoran Margaron, Jean-François Cote, Luke MacQueen, Michael D. Buschmann, Hassan Fahmi, Qin Shi, Karim Maghni, Julio C. Fernandes and Mohamed Benderdour

Article (2010)

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Abstract

INTRODUCTION: Objectives were to investigate whether interactions between human osteoarthritic chondrocytes and 4-hydroxynonenal (HNE)-modified type II collagen (Col II) affect cell phenotype and functions and to determine the protective role of carnosine (CAR) treatment in preventing these effects. METHODS: Human Col II was treated with HNE at different molar ratios (MR) (1:20 to 1:200; Col II:HNE). Articular chondrocytes were seeded in HNE/Col II adduct-coated plates and incubated for 48 hours. Cell morphology was studied by phase-contrast and confocal microscopy. Adhesion molecules such as intercellular adhesion molecule-1 (ICAM-1) and alpha1beta1 integrin at protein and mRNA levels were quantified by Western blotting, flow cytometry and real-time reverse transcription-polymerase chain reaction. Cell death, caspases activity, prostaglandin E2 (PGE2), metalloproteinase-13 (MMP-13), mitogen-activated protein kinases (MAPKs) and nuclear factor-kappa B (NF-kappaB) were assessed by commercial kits. Col II, cyclooxygenase-2 (COX-2), MAPK, NF-kappaB-p65 levels were analyzed by Western blotting. The formation of alpha1beta1 integrin-focal adhesion kinase (FAK) complex was revealed by immunoprecipitation. RESULTS: Col II modification by HNE at MR approximately 1:20, strongly induced ICAM-1, alpha1beta1 integrin and MMP-13 expression as well as extracellular signal-regulated kinases 1 and 2 (ERK1/2) and NF-kappaB-p65 phosphorylation without impacting cell adhesion and viability or Col II expression. However, Col II modification with HNE at MR approximately 1:200, altered chondrocyte adhesion by evoking cell death and caspase-3 activity. It inhibited alpha1beta1 integrin and Col II expression as well as ERK1/2 and NF-kappaB-p65 phosphorylation, but, in contrast, markedly elicited PGE2 release, COX-2 expression and p38 MAPK phosphorylation. Immunoprecipitation assay revealed the involvement of FAK in cell-matrix interactions through the formation of alpha1beta1 integrin-FAK complex. Moreover, the modification of Col II by HNE at a 1:20 or approximately 1:200 MR affects parameters of the cell shape. All these effects were prevented by CAR, an HNE-trapping drug. CONCLUSIONS: Our novel findings indicate that HNE-binding to Col II results in multiple abnormalities of chondrocyte phenotype and function, suggesting its contribution in osteoarthritis development. CAR was shown to be an efficient HNE-snaring agent capable of counteracting these outcomes.

Uncontrolled Keywords

Aged; Aldehydes/*metabolism; Blotting, Western; Carnosine/pharmacology; Cell Adhesion Molecules/drug effects/*metabolism; Cell Separation; Cells, Cultured; Chondrocytes/drug effects/*metabolism/pathology; Collagen Type II/*metabolism; Extracellular Matrix/drug effects/metabolism/pathology; Flow Cytometry; Fluorescent Antibody Technique; Gene Expression Profiling; Humans; Immunoprecipitation; Microscopy, Confocal; Osteoarthritis/*metabolism/pathology; Phenotype; RNA, Messenger/analysis; Reverse Transcriptase Polymerase Chain Reaction; Signal Transduction/drug effects/physiology

Subjects: 1800 Chemical engineering > 1800 Chemical engineering
1800 Chemical engineering > 1802 Biochemical engineering
Department: Department of Chemical Engineering
Funders: Canadian Institutes of Health Research
PolyPublie URL: https://publications.polymtl.ca/4853/
Journal Title: Arthritis Research and Therapy (vol. 12, no. 5)
Publisher: Springer Nature
DOI: 10.1186/ar3173
Official URL: https://doi.org/10.1186/ar3173
Date Deposited: 08 Sep 2021 15:35
Last Modified: 11 Apr 2024 00:48
Cite in APA 7: El-Bikai, R., Welman, M., Margaron, Y., Cote, J.-F., MacQueen, L., Buschmann, M. D., Fahmi, H., Shi, Q., Maghni, K., Fernandes, J. C., & Benderdour, M. (2010). Perturbation of adhesion molecule-mediated chondrocyte-matrix interactions by 4-hydroxynonenal binding: implication in osteoarthritis pathogenesis. Arthritis Research and Therapy, 12(5). https://doi.org/10.1186/ar3173

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