ArticleArthritis research & therapy2014
Acid-sensing ion channel 3 decreases phosphorylation of extracellular signal-regulated kinases and induces synoviocyte cell death by increasing intracellular calcium.
Article in Arthritis research & therapy, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 33 citations in OpenAlex.
- pH sensing and inflammation: linking acidic microenvironments to immune reprogramming.Frontiers in immunology · 2026Review
- Pyroptosis in Skeleton Diseases: A Potential Therapeutic Target Based on Inflammatory Cell Death.International journal of molecular sciences · 2024Review
- Activation of ASIC3/ERK pathway by paeoniflorin improves intestinal fluid metabolism and visceral sensitivity in slow transit constipated rats.The Kaohsiung journal of medical sciences · 2024Article
- Complex alterations in inflammatory pain and analgesic sensitivity in young and ageing female rats: involvement of ASIC3 and Nav1.8 in primary sensory neurons.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2024Article
- Calcium-Permeable Channels Cooperation for Rheumatoid Arthritis: Therapeutic Opportunities.Biomolecules · 2022Review
- Normalization of Neuroinflammation: A New Strategy for Treatment of Persistent Pain and Memory/Emotional Deficits in Chronic Pain.Journal of inflammation research · 2022Review
- Acid-sensing ion channel 3: An analgesic target.Channels (Austin, Tex.) · 2021Review
- Apoptosis, Autophagy, NETosis, Necroptosis, and Pyroptosis Mediated Programmed Cell Death as Targets for Innovative Therapy in Rheumatoid Arthritis.Frontiers in immunology · 2021Review
- In silico screening of GMQ-like compounds reveals guanabenz and sephin1 as new allosteric modulators of acid-sensing ion channel 3.Biochemical pharmacology · 2020Article
- An overview of carbonic anhydrases and membrane channels of synoviocytes in inflamed joints.Journal of enzyme inhibition and medicinal chemistry · 2019Review
- Acid-sensing ion channel 1a mediates acid-induced inhibition of matrix metabolism of rat articular chondrocytes via the MAPK signaling pathway.Molecular and cellular biochemistry · 2018Article
- ASIC1 and ASIC3 contribute to acidity-induced EMT of pancreatic cancer through activating CaCell death & disease · 2017Article
- Novel Insights into Acid-Sensing Ion Channels: Implications for Degenerative Diseases.Aging and disease · 2016Review
- ASIC3 Is Required for Development of Fatigue-Induced Hyperalgesia.Molecular neurobiology · 2016Article
- ASICs Mediate Pain and Inflammation in Musculoskeletal Diseases.Physiology (Bethesda, Md.) · 2015Review
- The dichotomized role for acid sensing ion channels in musculoskeletal pain and inflammation.Neuropharmacology · 2015Review
- Peripheral mechanisms of arthritic pain: A proposal to leverage large animals forNeurobiology of pain (Cambridge, Mass.)Review
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
Abstract
introductionAcid-sensing ion channel 3 (ASIC3) is expressed in synoviocytes, activated by decreases in pH, and reduces inflammation in animal models of inflammatory arthritis. The purpose of the current study was to characterize potential mechanisms underlying the control of inflammation by ASIC3 in fibroblast-like synoviocytes (FLS).
methodsExperiments were performed in cultured FLS from wild-type (WT) and ASIC3-/- mice, ASIC1-/- mice, and people with rheumatoid arthritis. We assessed the effects of acidic pH with and without interleukin-1β on FLS and the role of ASICs in modulating intracellular calcium [Ca(2+)](i), mitogen activated kinase (MAP kinase) expression, and cell death. [Ca(2+)](i) was assessed by fluorescent calcium imaging, MAP kinases were measured by Western Blots; ASIC, cytokine and protease mRNA expression were measured by quantitative PCR and cell death was measured with a LIVE/DEAD assay.
resultsAcidic pH increased [Ca(2+)](i) and decreased p-ERK expression in WT FLS; these effects were significantly smaller in ASIC3-/- FLS and were prevented by blockade of [Ca(2+)]i. Blockade of protein phosphatase 2A (PP2A) prevented the pH-induced decreases in p-ERK. In WT FLS, IL-1β increases ASIC3 mRNA, and when combined with acidic pH enhances [Ca(2+)](i), p-ERK, IL-6 and metalloprotienase mRNA, and cell death. Inhibitors of [Ca(2+)](i) and ERK prevented cell death induced by pH 6.0 in combination with IL-1β in WT FLS.
conclusionsDecreased pH activates ASIC3 resulting in increased [Ca(2+)](i), and decreased p-ERK. Under inflammatory conditions, acidic pH results in enhanced [Ca(2+)](i) and phosphorylation of extracellular signal-regulated kinase that leads to cell death. Thus, activation of ASIC3 on FLS by acidic pH from an inflamed joint could limit synovial proliferation resulting in reduced accumulation of inflammatory mediators and subsequent joint damage.
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