Acidic pH Promotes Intervertebral Disc Degeneration: Acid-Sensing Ion Channel -3 as a Potential Therapeutic Target
Open accessAbstract
The aetiology of intervertebral disc (IVD) degeneration remains poorly understood. Painful IVD degeneration is associated with an acidic intradiscal pH but the response of NP cells to this aberrant microenvironmental factor remains to be fully characterised. The aim here was to address the hypothesis that acidic pH, similar to that found in degenerate IVDs, leads to the altered cell/functional phenotype observed during IVD degeneration, and to investigate the involvement of acid-sensing ion channel (ASIC) -3 in the response. Human NP cells were treated with a range of pH, from that of a non-degenerate (pH 7.4 and 7.1) through to mildly degenerate (pH 6.8) and severely degenerate IVD (pH 6.5 and 6.2). Increasing acidity of pH caused a decrease in cell proliferation and viability, a shift towards matrix catabolism and increased expression of proinflammatory cytokines and pain-related factors. Acidic pH resulted in an increase in ASIC-3 expression. Importantly, inhibition of ASIC-3 prevented the acidic pH induced proinflammatory and pain-related phenotype in NP cells. Acidic pH causes a catabolic and degenerate phenotype in NP cells which is inhibited by blocking ASIC-3 activity, suggesting that this may be a useful therapeutic target for treatment of IVD degeneration.
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Medium acidification during in vitro cell culture can initiate pro-inflammatory signaling responses in human aortic smooth muscle cells and cells of the human nucleus pulposus.
“Medium acidification during in vitro cell culture can also initiate pro-inflammatory signaling responses in human aortic smooth muscle cells (Tomura et al., 2005) and cells of the human nucleus pulposus (Gilbert et al., 2016).”
From Toward Best Practices for Controlling Mammalian Cell Culture Environments (2022) · cites this paper as Gilbert et al., 2016
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- Authors
- Gilbert, H. T. J., Hodson, N., Baird, P., Richardson, S. M., & Hoyland, J. A.
- Affiliations
- Wellcome Centre for Cell-Matrix Research (GB)
- University of Manchester (GB)
- Manchester Academic Health Science Centre (GB)
- Corresponding author
- Hoyland, Judith A.
- Venue
- Scientific Reports
- Published
- 2016-11-17
- Volume
- 6
- Issue
- 1
- Pages
- 37360-37360
- ISSN
- 2045-2322 (ISSN-L)
- PMC
- PMC5112591
- OpenAlex
- W2557122684
- Cited by
- 140
- References
- 61
- Citations by year
- 2026: 16 · 2025: 12 · 2024: 16 · 2023: 12 · 2022: 27 · 2021: 16 · 2020: 14 · 2019: 12 · 2018: 11 · 2017: 4
- FWCI
- 8.18
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Scientific Reports (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Research Explorer (The University of Manchester) (publishedVersion, cc-by)
- University of Birmingham Research Portal (University of Birmingham) (submittedVersion, other-oa)
- Funders
- National Institute for Health and Care Research
- Versus Arthritis
- Directorate for Biological Sciences
- Biotechnology and Biological Sciences Research Council
- Topics
- Health Sciences › Medicine › Pathology and Forensic Medicine › Spine and Intervertebral Disc Pathology
- Health Sciences › Medicine › Rheumatology › Osteoarthritis Treatment and Mechanisms
- Health Sciences › Medicine › Physiology › Pain Mechanisms and Treatments
- Keywords
- intervertebral disc degeneration, low pH, ASIC3, nucleus pulposus cells, matrix catabolism, inflammatory cytokines, cell proliferation, cell viability, therapeutic target
- MeSH terms
- Nucleus Pulposus, Cell Survival, Cells, Cultured, Cnidarian Venoms, Drug Evaluation, Preclinical, Female, Humans, Hydrogen-Ion Concentration, Male, Middle Aged, Transcriptional Activation, Cytokines, Brain-Derived Neurotrophic Factor, Nerve Growth Factor, Cell Proliferation, Intervertebral Disc Degeneration, Molecular Targeted Therapy, Acid Sensing Ion Channels, Acid Sensing Ion Channel Blockers
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