Cambre, Isabelle and Gaublomme, Djoere and Burssens, Arne and Jacques, Peggy and Schryvers, Nadia and De Muynck, Amelie and Meuris, Leander and Lambrecht, Stijn and Carter, Shea and de Bleser, Pieter and Saeys, Yvan and Van Hoorebeke, Luc and Kollias, George and Mack, Matthias and Simoens, Paul and Lories, Rik and Callewaert, Nico and Schett, Georg and Elewaut, Dirk (2018) Mechanical strain determines the site-specific localization of inflammation and tissue damage in arthritis. NATURE COMMUNICATIONS, 9: 4613. ISSN 2041-1723,
Full text not available from this repository. (Request a copy)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.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | RHEUMATOID-ARTHRITIS; JOINT; AUTOIMMUNITY; OSTEOCLASTS; RESOLUTION; MONOCYTES; DISEASE; CELLS; TNF; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Abteilung für Nephrologie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 10 Oct 2019 06:52 |
| Last Modified: | 10 Oct 2019 06:52 |
| URI: | https://pred.uni-regensburg.de/id/eprint/13556 |
Actions (login required)
 |
View Item |
