Pathogenic role of basic calcium phosphate crystals in destructive arthropathies
Autor: | Nathalie Busso, Geraldine M. McCarthy, Peter L. E. M. van Lent, Christelle Nguyen, Arnaud Dessombz, Frédéric Lioté, Sonia Nasi, Alexander So, Annette Ives, Hang-Korng Ea, Brigitte Jolles-Haeberli, Michel Daudon, Daniel Van Linthoudt, Véronique Chobaz, Dominique Bazin |
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Přispěvatelé: | Os et articulations, Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Lausanne (UNIL), Radboud University Medical Center [Nijmegen], Service d'Explorations fonctionnelles multidisciplinaires [CHU Tenon], CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Laboratoire de Physique des Solides (LPS), Centre National de la Recherche Scientifique (CNRS)-Université Paris-Sud - Paris 11 (UP11), Spectroscopie, Modélisation, Interfaces pour L'Environnement et la Santé (SMiLES), Laboratoire de Chimie de la Matière Condensée de Paris (LCMCP), Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Collège de France (CdF (institution))-Institut de Chimie du CNRS (INC)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Collège de France (CdF (institution))-Institut de Chimie du CNRS (INC), Mater Misericordiae University Hospital, HAL-UPMC, Gestionnaire, Université de Lausanne = University of Lausanne (UNIL), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Université Paris-Sud - Paris 11 (UP11)-Centre National de la Recherche Scientifique (CNRS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Collège de France (CdF (institution))-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Collège de France (CdF (institution))-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Mater Misericordiae University Hospital (The Mater Hospital), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU) |
Rok vydání: | 2013 |
Předmět: |
Calcium Phosphates
Pathology Anatomy and Physiology Mouse Arthritis Apoptosis Osteoarthritis Mice 0302 clinical medicine Spectroscopy Fourier Transform Infrared Musculoskeletal System Mice Knockout 0303 health sciences [SDV.MHEP.RSOA] Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system Multidisciplinary biology Chemistry Inflammasome Animal Models Immunohistochemistry Infection and autoimmunity Auto-immunity transplantation and immunotherapy [NCMLS 1] medicine.anatomical_structure [SDV.MHEP.RSOA]Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system Medicine Female Crystallization medicine.drug Research Article medicine.medical_specialty Science Real-Time Polymerase Chain Reaction Chondrocyte Proinflammatory cytokine 03 medical and health sciences Model Organisms Rheumatology Synovitis medicine Animals Biology 030304 developmental biology DNA Primers 030203 arthritis & rheumatology Base Sequence Cartilage Macrophages medicine.disease Molecular biology Mice Inbred C57BL Proteoglycan biology.protein Interleukin-1 |
Zdroj: | PLoS One, 8 PLoS ONE PLoS ONE, Public Library of Science, 2013, 8 (2), pp.e57352. ⟨10.1371/journal.pone.0057352.s001⟩ PLoS ONE, 2013, 8 (2), pp.e57352. ⟨10.1371/journal.pone.0057352.s001⟩ PLoS One, 8, 2 Plos One, vol. 8, no. 2, pp. e57352 PLOS One PLoS ONE, Vol 8, Iss 2, p e57352 (2013) |
ISSN: | 1932-6203 |
Popis: | Contains fulltext : 118931.pdf (Publisher’s version ) (Open Access) BACKGROUND: basic calcium phosphate (BCP) crystals are commonly found in osteoarthritis (OA) and are associated with cartilage destruction. BCP crystals induce in vitro catabolic responses with the production of metalloproteases and inflammatory cytokines such as interleukin-1 (IL-1). In vivo, IL-1 production induced by BCP crystals is both dependant and independent of NLRP3 inflammasome. We aimed to clarify 1/ the role of BCP crystals in cartilage destruction and 2/ the role of IL-1 and NLRP3 inflammasome in cartilage degradation related to BCP crystals. METHODOLOGY PRINCIPAL FINDINGS: synovial membranes isolated from OA knees were analysed by alizarin Red and FTIR. Pyrogen free BCP crystals were injected into right knees of WT, NLRP3 -/-, ASC -/-, IL-1alpha -/- and IL-1beta-/- mice and PBS was injected into left knees. To assess the role of IL-1, WT mice were treated by intra-peritoneal injections of anakinra, the IL-1Ra recombinant protein, or PBS. Articular destruction was studied at d4, d17 and d30 assessing synovial inflammation, proteoglycan loss and chondrocyte apoptosis. BCP crystals were frequently found in OA synovial membranes including low grade OA. BCP crystals injected into murine knee joints provoked synovial inflammation characterized by synovial macrophage infiltration that persisted at day 30, cartilage degradation as evidenced by loss of proteoglycan staining by Safranin-O and concomitant expression of VDIPEN epitopes, and increased chondrocyte apoptosis. BCP crystal-induced synovitis was totally independent of IL-1alpha and IL-1beta signalling and no alterations of inflammation were observed in mice deficient for components of the NLRP3-inflammasome, IL-1alpha or IL-1beta. Similarly, treatment with anakinra did not prevent BCP crystal effects. In vitro, BCP crystals elicited enhanced transcription of matrix degrading and pro-inflammatory genes in macrophages. CONCLUSIONS SIGNIFICANCE: intra-articular BCP crystals can elicit synovial inflammation and cartilage degradation suggesting that BCP crystals have a direct pathogenic role in OA. The effects are independent of IL-1 and NLRP3 inflammasome. |
Databáze: | OpenAIRE |
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