Extracellular mitochondrial DNA and oxidatively damaged DNA in synovial fluid of patients with rheumatoid arthritis
Open accessAbstract
We investigated whether plasma and synovial fluid (SF) samples from patients with rheumatoid arthritis (RA) contained extracellular mitochondrial DNA (mtDNA) or the oxidatively damaged DNA adduct 8-hydroxy-2'-deoxyguanosine (8-oxodG). Moreover, we correlated the laboratory findings of the patients with RA with their levels of mtDNA and 8-oxodG. SF and plasma samples from 54 patients with RA, SF from 30 non-arthritic control subjects, and plasma from 22 healthy volunteers were collected. The samples were subjected to polymerase chain reaction (PCR) using mitochondrial genomic primers, and the products were analyzed by SDS-polyacrylamide-gel electrophoresis. The intensities of the PCR-amplified bands were quantified and normalized to a reference sample. Furthermore, the SF samples were assayed by enzyme-linked immunosorbent assay for 8-oxodG. Extracellular PCR-amplifiable mtDNA was detected in the SF of 38 of 54 (70%) patients with RA, but not in any of the SF controls. PCR-amplifiable mtDNA was detected in the plasma of 30 of 54 (56%) of patients with RA and in 6 of 22 (27%) of the healthy volunteers. The levels of mtDNA in the plasma and SF samples of patients with RA were significantly higher (P < 0.0001) than in the respective control samples. The presence of both mtDNA and 8-oxodG in SF was significantly correlated with the presence of rheumatoid factor in the patients with RA. Extracellular mtDNA and oxidized DNA were detected in the SF of the great majority of patients with RA, but were absent or present at low levels in the control SF. These findings indicate that endogenous nucleic acid compounds might participate in joint inflammation by activating immune cells in the joints to produce proinflammatory cytokines.
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Circulating mtDNA, which can stimulate TLR9, is present in various inflammatory conditions including RA, SLE, Sjögren syndrome, cancers, neurodegenerative diseases, cardiovascular disease, type 2 diabetes, HIV, liver injuries, traumas, corrosive injuries, sepsis, ageing, and stress.
“Circulating mtDNA, which can stimulate TLR9 signalling, is present in various inflammatory conditions, including RA152,153, SLE154, Sjögren syndrome155, cancers156,157, neurodegenerative diseases158–161, cardiovascular disease162, type 2 diabetes163,164, HIV165, liver injuries166, traumas167, corrosive injuries168, sepsis169, ageing170 and stress171,172.”
From The role of mitochondria in rheumatic diseases (2022) · cites this paper as [153]
Extracellular mtDNA is associated with various pathologies, including trauma, burn injury, cancer, and rheumatoid arthritis.
“As extracellular mtDNA is reportedly associated with various pathologies, including trauma25,26, burn injury27, cancer28 and rheumatoid arthritis17,29”
From Anti-mitochondrial autoantibodies in systemic lupus erythematosus and their association with disease manifestations (2019) · cites this paper as [29]
mtDNA is present at significantly higher levels in plasma and synovial fluid from patients with rheumatoid arthritis.
“mtDNA was shown to be present at significantly higher levels in plasma and synovial fluid from patients with rheumatoid arthritis, a condition characterized by chronic inflammation and that is more prevalent in older age (Hajizadeh et al., 2003).”
From Cytoplasmic DNA: sources, sensing, and role in aging and disease (2021) · cites this paper as Hajizadeh et al., 2003
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- Authors
- Hajizadeh, S., DeGroot, J., TeKoppele, J. M., Tarkowski, A., & Collins, L. V.
- Affiliations
- University of Gothenburg (SE)
- Netherlands Organisation for Applied Scientific Research (NL)
- Corresponding author
- Hajizadeh, Shahin
- Venue
- Arthritis Res Ther
- Published
- 2003-06-25
- Volume
- 5
- Issue
- 5
- Pages
- R234-40
- ISSN
- 1478-6354 (ISSN-L)
- PMC
- PMC193725
- OpenAlex
- W2112472085
- Cited by
- 196
- References
- 25
- Citations by year
- 2026: 10 · 2025: 13 · 2024: 13 · 2023: 15 · 2022: 20 · 2021: 17 · 2020: 12 · 2019: 18 · 2018: 14 · 2017: 12 · 2016: 7 · 2015: 4 · 2014: 9 · 2013: 3 · 2012: 6
- FWCI
- 2.32
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Arthritis Research & Therapy (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion, other-oa)
- PubMed Central (publishedVersion, other-oa)
- PubMed (publishedVersion)
- Funders
- Medical Research Council
- Topics
- Health Sciences › Medicine › Rheumatology › Rheumatoid Arthritis Research and Therapies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Health Sciences › Medicine › Rheumatology › Systemic Lupus Erythematosus Research
- Keywords
- rheumatoid arthritis, oxidative DNA damage, 8-hydroxy-2'-deoxyguanosine, synovial fluid, plasma, rheumatoid factor, joint inflammation, inflammatory cytokines
- MeSH terms
- 8-Hydroxy-2'-Deoxyguanosine, Arthritis, Rheumatoid, Deoxyguanosine, DNA, DNA Damage, DNA, Mitochondrial, Extracellular Space, Female, Humans, Male, Middle Aged, Oxidation-Reduction, Rheumatoid Factor, Synovial Fluid, Polymerase Chain Reaction, DNA Adducts
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