Effect of M3 muscarinic acetylcholine receptor deficiency on collagen antibody-induced arthritis

Arthritis Research & Therapy
Janet BeckmannKatrin Susanne Lips

Abstract

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. 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. 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 chemoattract...Continue Reading

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Citations

Jan 30, 2018·The Journal of Pathology·Yoshinori YasudaYoshihisa Sugimura
Jan 18, 2019·International Journal of Molecular Sciences·Katarzyna D SluzalskaJuergen Steinmeyer
Feb 12, 2019·Bioelectronics in Medicine·Alexandre KanashiroLuis Ulloa
Jul 30, 2017·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Chang Hyun JinJin-Baek Kim

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Methods Mentioned

BETA
PCR
FACS
protein assay
ELISA
Enzyme-linked immunosorbent assay
transmission electron microscopy

Software Mentioned

GraphPad
FACS Diva
GraphPad Prism

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