TY  - JOUR
A1  - Beckmann, Janet
A1  - Dittmann, Nicole
A1  - Schütz, Iris
A1  - Klein, Jochen
A1  - Lips, Katrin Susanne
T1  - Effect of M3 muscarinic acetylcholine receptor deficiency on collagen antibody-induced arthritis
T2  - Arthritis Research & Therapy
N2  - Background: There is increasing evidence that the non-neuronal cholinergic system might be of importance for the pathology of rheumatoid arthritis. The role of M3 muscarinic acetylcholine receptor (M3R) in this regard has, however, not been investigated to date. Thus, in the present study we analyzed if M3R deficiency might have a protective effect on experimentally induced arthritis.
Methods: Collagen antibody-induced arthritis (CAIA) was evoked in M3R-deficient (M3R −/− ) mice and wild-type (WT) littermates. Severity of arthritis was assessed by scoring of paw swelling. The joints of arthritic and nonarthritic animals were analyzed for histopathological changes regarding synovial tissue, cartilage degradation and bone destruction. Further, gene expression analysis of respective markers was performed. Systemic and local inflammatory response was determined by flow cytometry and immunohistochemistry for leukocytes as well as mRNA and protein measurements for pro-inflammatory cytokines and chemokines.
Results: In arthritic M3R −/− mice the number of leukocytes, specifically neutrophils, was enhanced even though clinical arthritis score was not significantly different between WT and M3R −/− mice with CAIA. In M3R −/− mice, levels of neutrophil chemoattractant chemokine C-X-C-motif ligand 2 (CXCL2) as well as the pro-inflammatory cytokine interleukin-6 were already strongly increased in mice with low arthritis score, whereas WT mice only showed prominent expression of these markers when reaching high arthritis scores. Furthermore, arthritic M3R −/− mice displayed a stronger degradation of collagen II in the articular cartilage and, most strikingly, histopathological evaluation revealed more severe bone destruction in arthritic mice with M3R deficiency compared to WT littermates. Moreover, in M3R −/− mice, gene expression of markers for bone degradation (matrix metalloproteinase 13, cathepsin K and receptor activator of nuclear factor-κB ligand) was already increased in mice with low arthritis score.
Conclusions: Taken together, the present study shows that while M3R −/− mice were not protected from CAIA, they had a tendency toward a higher inflammatory response after arthritis induction than WT mice. Further, arthritis-induced joint destruction was significantly stronger in mice with M3R deficiency, indicating that stimulation of M3R might have protective effects on arthritis.
KW  - Muscarinic acetylcholine receptor
KW  - Non-neuronal cholinergic system
KW  - Rheumatoid arthritis
KW  - Collagen antibody-induced arthritis
KW  - Joint destruction
KW  - Synovial inflammation
Y1  - 2016
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/37392
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-373921
SN  - 1465-9913
SN  - 1478-6362
N1  - © 2016 Beckmann et al. Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
VL  - 18
IS  - 17
SP  - 1
EP  - 16
PB  - BioMed Central
CY  - London
ER  -