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Nat Commun. 2018 Nov 5;9(1):4613. doi: 10.1038/s41467-018-06933-4.

Mechanical strain determines the site-specific localization of inflammation and tissue damage in arthritis.

Author information

1
Unit for Molecular Immunology and Inflammation, VIB Inflammation Research Center (IRC), Technologiepark 927, 9052, Ghent, Belgium.
2
Department of Rheumatology, Ghent University, Ghent University Hospital, De Pintelaan 185, 9000, Ghent, Belgium.
3
Department of Orthopaedics and Traumatology, Ghent University Hospital, De Pintelaan 185, 9000, Ghent, Belgium.
4
UGCT-Department of Physics and Astronomy, Ghent University, Proeftuinstraat 86, 9000, Ghent, Belgium.
5
Unit of Medical Biotechnology, VIB Inflammation Research Center (IRC), VIB, Technologiepark 927, 9052, Ghent, Belgium.
6
Laboratory for Protein Biochemistry and Biomolecular Engineering, Department of Biochemistry and Microbiology, Ghent University, Technologiepark 927, 9000, Ghent, Belgium.
7
Department of Development and Regeneration, Laboratory of Tissue Homeostasis and Disease, Skeletal Biology and Engineering Research Center, KU Leuven, Herestraat 49, 3000, Leuven, Belgium.
8
Division of Rheumatology, University Hospitals Leuven, Herestraat 49, 3000, Leuven, Belgium.
9
Data Mining and Modeling for Biomedicine, VIB Center for Inflammation Research, Technologiepark 927, 9052, Ghent, Belgium.
10
Division of Immunology, Biomedical Sciences Research Center 'Alexander Fleming', 34, Fleming Street, 16672, Vari, Attica, Greece.
11
Department of Experimental Physiology, School of Medicine, National and Kapodistrian University of Athens, 75 Mikras Asias Street, 11527, Goudi, Athens, Greece.
12
Deparment of Internal Medicine II - Nephrology, University Hospital Regensburg, 93402, Regensburg, Germany.
13
Department of Morphology, Faculty of Veterinary Medicine, Ghent University, Salisburylaan 133, 9820, Merelbeke, Belgium.
14
Department of Internal Medicine 3, Rheumatology and Immunology, Friedrich Alexander University of Erlangen-Nuremberg and Universitatsklinikum, Ulmenweg 18, 91054, Erlangen, Germany.
15
Unit for Molecular Immunology and Inflammation, VIB Inflammation Research Center (IRC), Technologiepark 927, 9052, Ghent, Belgium. Dirk.Elewaut@UGent.be.
16
Department of Rheumatology, Ghent University, Ghent University Hospital, De Pintelaan 185, 9000, Ghent, Belgium. Dirk.Elewaut@UGent.be.

Abstract

Many pro-inflammatory pathways leading to arthritis have global effects on the immune system rather than only acting locally in joints. The reason behind the regional and patchy distribution of arthritis represents a longstanding paradox. Here we show that biomechanical loading acts as a decisive factor in the transition from systemic autoimmunity to joint inflammation. Distribution of inflammation and erosive disease is confined to mechano-sensitive regions with a unique microanatomy. Curiously, this pathway relies on stromal cells but not adaptive immunity. Mechano-stimulation of mesenchymal cells induces CXCL1 and CCL2 for the recruitment of classical monocytes, which can differentiate into bone-resorbing osteoclasts. Genetic ablation of CCL2 or pharmacologic targeting of its receptor CCR2 abates mechanically-induced exacerbation of arthritis, indicating that stress-induced chemokine release by mesenchymal cells and chemo-attraction of monocytes determines preferential homing of arthritis to certain hot spots. Thus, mechanical strain controls the site-specific localisation of inflammation and tissue damage in arthritis.

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