Synovial macrophages promote TGF-β signaling and protect against influx of S100A8/S100A9-producing cells after intra-articular injections of oxidized low-density lipoproteins.

Autor: de Munter W; Experimental Rheumatology, Radboud University Medical Center, Nijmegen, The Netherlands. Electronic address: Wouter.deMunter@radboudumc.nl., Geven EJ; Experimental Rheumatology, Radboud University Medical Center, Nijmegen, The Netherlands. Electronic address: Edwin.Geven@radboudumc.nl., Blom AB; Experimental Rheumatology, Radboud University Medical Center, Nijmegen, The Netherlands. Electronic address: Arjen.Blom@radboudumc.nl., Walgreen B; Experimental Rheumatology, Radboud University Medical Center, Nijmegen, The Netherlands. Electronic address: Birgitte.Walgreen@radboudumc.nl., Helsen MM; Experimental Rheumatology, Radboud University Medical Center, Nijmegen, The Netherlands. Electronic address: Monique.Helsen@radboudumc.nl., Joosten LA; Department of Internal Medicine and Radboud Center for Infectious Diseases (RCI), Radboud University Medical Center, Nijmegen, The Netherlands. Electronic address: Leo.Joosten@radboudumc.nl., Roth J; Institute of Immunology, University of Muenster, Muenster, Germany. Electronic address: rothj@uni-muenster.de., Vogl T; Institute of Immunology, University of Muenster, Muenster, Germany. Electronic address: vogl@uni-muenster.de., van de Loo FA; Experimental Rheumatology, Radboud University Medical Center, Nijmegen, The Netherlands. Electronic address: Fons.vandeLoo@radboudumc.nl., Koenders MI; Experimental Rheumatology, Radboud University Medical Center, Nijmegen, The Netherlands. Electronic address: Marije.Koenders@radboudumc.nl., van den Berg WB; Experimental Rheumatology, Radboud University Medical Center, Nijmegen, The Netherlands. Electronic address: Wim.vandenBerg@radboudumc.nl., van der Kraan PM; Experimental Rheumatology, Radboud University Medical Center, Nijmegen, The Netherlands. Electronic address: Peter.vanderKraan@radboudumc.nl., van Lent PL; Experimental Rheumatology, Radboud University Medical Center, Nijmegen, The Netherlands. Electronic address: Peter.vanLent@radboudumc.nl.
Jazyk: angličtina
Zdroj: Osteoarthritis and cartilage [Osteoarthritis Cartilage] 2017 Jan; Vol. 25 (1), pp. 118-127. Date of Electronic Publication: 2016 Aug 08.
DOI: 10.1016/j.joca.2016.07.020
Abstrakt: Objective: Low-density lipoproteins (LDL) in inflamed synovium is oxidized and taken-up by synoviocytes. In this study, we investigate whether direct injection of oxidized LDL (oxLDL) into a normal murine knee joint induces joint pathology and whether synovial macrophages are involved in that process.
Design: Synovium was obtained from end-stage osteoarthritis (OA) patients in order to analyze LDL-uptake. Murine knee joints were injected five consecutive days with oxLDL, LDL, or vehicle (phosphate buffered saline (PBS)). This procedure was repeated in mice depleted of synovial macrophages by intra-articular injection of clodronate liposomes 7 days prior to the consecutive injections. Joint pathology was investigated by immunohistochemistry, flow cytometry (FCM) and synovial RNA expression and protein production.
Results: Synovial tissue of OA patients showed extensive accumulation of apolipoprotein B. Multiple injections of oxLDL in murine knee joints significantly increased TGF-β activity in synovial wash-outs, but did not induce catabolic or inflammatory processes. In contrast, repeated injections of oxLDL in macrophage-depleted knee joints led to increased synovial thickening in combination with significantly upregulated protein and RNA levels of CCL2 and CCL3. FCM-analyses revealed increased presence of monocytes and neutrophils in the synovium, which was confirmed by immunohistochemistry. Also protein levels of S100A8/A9 were significantly increased in synovial wash-outs of oxLDL-injected joints, as was expression of aggrecanase-induced neo-epitopes. Interestingly, no raise in TGF-β concentrations was measured in macrophage-depleted joints.
Conclusions: OxLDL can affect joint pathology, since synovial macrophages promote anabolic processes after oxLDL injections. In absence of synovial macrophages, however, oxLDL induces production of pro-inflammatory mediators and aggrecanase activity combined with increased influx of monocytes and neutrophils.
(Copyright © 2016 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE
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