BACKGROUND: There is increasing evidence that the non-neuronal cholinergic system might be of importance for the pathology of @entity309 . The role of M3 muscarinic @entity934 receptor ( @entity56014 ) in this regard has, however, not been investigated to date. Thus, in the present study we analyzed if @entity942 might have a protective effect on experimentally induced @entity625 . METHODS: Collagen antibody-induced @entity625 (CAIA) was evoked in @entity942 (M3R(-/-)) @entity19 and @entity164 ( @entity164 ) littermates. Severity of @entity625 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 @entity79 . 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(-/-) @entity19 the number of leukocytes, specifically neutrophils, was enhanced even though clinical @entity625 score was not significantly different between @entity164 and M3R(-/-) @entity19 with CAIA. In @entity56014 (-/-) @entity19 , levels of neutrophil chemoattractant @entity9701 ( @entity9701 ) as well as the pro-inflammatory cytokine @entity777 were already strongly increased in @entity19 with low @entity625 score, whereas @entity164 @entity19 only showed prominent expression of these markers when reaching high @entity625 scores. Furthermore, arthritic M3R(-/-) @entity19 displayed a stronger degradation of collagen II in the articular cartilage and, most strikingly, histopathological evaluation revealed more severe @entity79 in arthritic @entity19 with @entity942 compared to @entity164 littermates. Moreover, in M3R(-/-) @entity19 , gene expression of markers for bone degradation ( @entity5782 , cathepsin K and receptor activator of nuclear factor-kB ligand) was already increased in @entity19 with low @entity625 score. CONCLUSIONS: Taken together, the present study shows that while M3R(-/-) @entity19 were not protected from CAIA, they had a tendency toward a higher inflammatory response after @entity625 induction than @entity164 @entity19 . Further, @entity625 -induced joint destruction was significantly stronger in @entity19 with @entity942 , indicating that stimulation of M3R might have protective effects on @entity625 .

Effect of M3 muscarinic XXXX receptor deficiency on collagen antibody-induced @entity625 .

@entity625 :: ('MESH:D001168', 'Disease') :: ['arthritis'] @entity56014 :: ('p|SUB|M|3|R', 'ProteinMutation') :: ['M3R'] @entity19 :: ('10090', 'Species') :: ['mice'] @entity79 :: ('MESH:D001847', 'Disease') :: ['bone destruction'] @entity9701 :: ('20310(Tax:10090)', 'Gene') :: ['CXCL2', 'chemokine C-X-C-motif ligand 2'] @entity777 :: ('16193(Tax:10090)', 'Gene') :: ['interleukin-6'] @entity164 :: ('MESH:D017827', 'Disease') :: ['WT', 'wild-type'] @entity5782 :: ('17386(Tax:10090)', 'Gene') :: ['matrix metalloproteinase 13'] @entity309 :: ('MESH:D001172', 'Disease') :: ['rheumatoid arthritis'] @entity942 :: ('MESH:D003677', 'Disease') :: ['M3R deficiency', 'M3R-deficient'] @entity934 :: ('MESH:D000109', 'Chemical') :: ['acetylcholine']
@entity934 :: (MESH:D000109,Chemical) :: ['acetylcholine']
