PMID- 23335302
OWN - NLM
STAT- MEDLINE
DCOM- 20130618
LR  - 20220330
IS  - 1529-0131 (Electronic)
IS  - 0004-3591 (Print)
IS  - 0004-3591 (Linking)
VI  - 65
IP  - 5
DP  - 2013 May
TI  - Acid-sensing ion channel 3 deficiency increases inflammation but decreases pain 
      behavior in murine arthritis.
PG  - 1194-202
LID - 10.1002/art.37862 [doi]
AB  - OBJECTIVE: Through its location on nociceptors, acid-sensing ion channel 3 
      (ASIC-3) is activated by decreases in pH and plays a significant role in 
      musculoskeletal pain. We recently showed that decreases in pH activate ASIC-3 
      located on fibroblast-like synoviocytes (FLS), which are key cells in the 
      inflammatory process. The purpose of this study was to test whether 
      ASIC-3-deficient mice with arthritis have altered inflammation and pain relative 
      to controls. METHODS: Collagen antibody-induced arthritis (CAIA) was generated by 
      injection of an anti-type II collagen antibody cocktail. Inflammation and pain 
      parameters in ASIC-3(-/-) and ASIC-3(+/+) mice were assessed. Disease severity 
      was assessed by determining clinical arthritis scores, measuring joint diameters, 
      analyzing joint histology, and assessing synovial gene expression by quantitative 
      polymerase chain reaction analysis. Cell death was assessed with a Live/Dead 
      assay of FLS in response to decreases in pH. Pain behaviors in the mice were 
      measured by examining withdrawal thresholds in the joints and paws and by 
      measuring their physical activity levels. RESULTS: Surprisingly, ASIC-3(-/-) mice 
      with CAIA demonstrated significantly increased joint inflammation, joint 
      destruction, and expression of interleukin-6 (IL-6), matrix metalloproteinase 3 
      (MMP-3), and MMP-13 in joint tissue as compared to ASIC-3(+/+) mice. ASIC-3(+/+) 
      FLS showed enhanced cell death when exposed to pH 6.0 in the presence of IL-1beta, 
      which was abolished in ASIC-3(-/-) FLS. Despite enhanced disease severity, 
      ASIC-3(-/-) mice did not develop mechanical hypersensitivity of the paw and 
      showed greater levels of physical activity. CONCLUSION: Our findings are 
      consistent with the hypothesis that ASIC-3 plays a protective role in the 
      inflammatory arthritides by limiting inflammation through enhanced synoviocyte 
      cell death, which reduces disease severity, and through the production of pain, 
      which reduces joint use.
CI  - Copyright (c) 2013 by the American College of Rheumatology.
FAU - Sluka, Kathleen A
AU  - Sluka KA
AD  - Department of Physical Therapy and Rehabilitation Science, University of Iowa 
      Carver College of Medicine, Iowa City 52242, USA. kathleen-sluka@uiowa.edu
FAU - Rasmussen, Lynn A
AU  - Rasmussen LA
FAU - Edgar, Meghan M
AU  - Edgar MM
FAU - O'Donnell, James M
AU  - O'Donnell JM
FAU - Walder, Roxanne Y
AU  - Walder RY
FAU - Kolker, Sandra J
AU  - Kolker SJ
FAU - Boyle, David L
AU  - Boyle DL
FAU - Firestein, Gary S
AU  - Firestein GS
LA  - eng
GR  - R01 AR053509/AR/NIAMS NIH HHS/United States
PT  - Journal Article
PL  - United States
TA  - Arthritis Rheum
JT  - Arthritis and rheumatism
JID - 0370605
RN  - 0 (ASIC3 protein, mouse)
RN  - 0 (Acid Sensing Ion Channels)
RN  - 0 (Interleukin-6)
RN  - EC 3.4.24.- (Matrix Metalloproteinases)
SB  - IM
MH  - Acid Sensing Ion Channels/*deficiency
MH  - Animals
MH  - Arthritis, Experimental/complications/*pathology/physiopathology
MH  - Arthritis, Rheumatoid/complications/*pathology/physiopathology
MH  - Behavior, Animal
MH  - Cell Death
MH  - Cell Survival
MH  - Female
MH  - Gene Expression
MH  - Hindlimb
MH  - Hyperalgesia
MH  - Interleukin-6/genetics/metabolism
MH  - Joints/metabolism/pathology/physiopathology
MH  - Male
MH  - Matrix Metalloproteinases/genetics/metabolism
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Pain/etiology/*pathology/physiopathology
MH  - Pain Measurement
MH  - Pain Threshold
MH  - Severity of Illness Index
MH  - Synovitis/etiology/*pathology/physiopathology
PMC - PMC3636153
MID - NIHMS433621
EDAT- 2013/01/22 06:00
MHDA- 2013/06/19 06:00
PMCR- 2014/05/01
CRDT- 2013/01/22 06:00
PHST- 2012/05/11 00:00 [received]
PHST- 2013/01/03 00:00 [accepted]
PHST- 2013/01/22 06:00 [entrez]
PHST- 2013/01/22 06:00 [pubmed]
PHST- 2013/06/19 06:00 [medline]
PHST- 2014/05/01 00:00 [pmc-release]
AID - 10.1002/art.37862 [doi]
PST - ppublish
SO  - Arthritis Rheum. 2013 May;65(5):1194-202. doi: 10.1002/art.37862.