SynthesisAnnals of the rheumatic diseases2023
A meta-analysis and a functional study support the influence of mtDNA variant m.16519C on the risk of rapid progression of knee osteoarthritis.
Synthesis in Annals of the rheumatic diseases, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
What it found
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Who cites it
12 citing papers in PubMed, 16 citations in OpenAlex.
- Mitochondria-targeted MXene-based nanozymes promote mitophagy and inhibit mtDNA-triggered cGAS/STING inflammation in osteoarthritis.Bioactive materials · 2026Article
- Article
- Exploring mitochondrial functions and dysfunctions in chondrocytes: toward the identification of novel therapies for osteoarthritis.Bone research · 2026Review
- Redox-Related Genetic and Biological Ageing Signals in Rapid Pain Progression of Knee Osteoarthritis: A Hypothesis-Generating Analysis in the Osteoarthritis Initiative.Antioxidants (Basel, Switzerland) · 2026Article
- Targeting the mitochondrial metabolite-dynamics-MDVs-MitoEVs axis: a new frontier in osteoarthritis management.Journal of translational medicine · 2026Review
- Autologous transplantation of mitochondria/rAAV IGF-I platforms in human osteoarthritic articular chondrocytes to treat osteoarthritis.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- SIRT3-PINK1-PKM2 axis prevents osteoarthritis via mitochondrial renewal and metabolic switch.Bone research · 2025Article
- The potential of mitochondrial transfer as the modifying therapy for osteoarthritis.Frontiers in cell and developmental biology · 2025Review
- From dysfunction to healing: advances in mitochondrial therapy for Osteoarthritis.Journal of translational medicine · 2024Review
- The role and intervention of mitochondrial metabolism in osteoarthritis.Molecular and cellular biochemistry · 2024Review
- Epigenetics in Knee Osteoarthritis: A 2020-2023 Update Systematic Review.Life (Basel, Switzerland) · 2024Review
- The Role of Genetics and Epigenetic Regulation in the Pathogenesis of Osteoarthritis.International journal of molecular sciences · 2023Review
Corrections and comments
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Authors and funding
17 authors at 1 institution in 1 country.
Funding
Abstract
objectivesTo identify mitochondrial DNA (mtDNA) genetic variants associated with the risk of rapid progression of knee osteoarthritis (OA) and to characterise their functional significance using a cellular model of transmitochondrial cybrids.
methodsThree prospective cohorts contributed participants. The osteoarthritis initiative (OAI) included 1095 subjects, the Cohort Hip and Cohort Knee included 373 and 326 came from the PROspective Cohort of Osteoarthritis from A Coruña. mtDNA variants were screened in an initial subset of 450 subjects from the OAI by in-depth sequencing of mtDNA. A meta-analysis of the three cohorts was performed. A model of cybrids was constructed to study the functional consequences of harbouring the risk mtDNA variant by assessing: mtDNA copy number, mitochondrial biosynthesis, mitochondrial fission and fusion, mitochondrial reactive oxygen species (ROS), oxidative stress, autophagy and a whole transcriptome analysis by RNA-sequencing.
resultsmtDNA variant m.16519C is over-represented in rapid progressors (combined OR 1.546; 95% CI 1.163 to 2.054; p=0.0027). Cybrids with this variant show increased mtDNA copy number and decreased mitochondrial biosynthesis; they produce higher amounts of mitochondrial ROS, are less resistant to oxidative stress, show a lower expression of the mitochondrial fission-related gene fission mitochondrial 1 and an impairment of autophagic flux. In addition, its presence modulates the transcriptome of cybrids, especially in terms of inflammation, where interleukin 6 emerges as one of the most differentially expressed genes.
conclusionsThe presence of the mtDNA variant m.16519C increases the risk of rapid progression of knee OA. Among the most modulated biological processes associated with this variant, inflammation and negative regulation of cellular process stand out. The design of therapies based on the maintenance of mitochondrial function is recommended.
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Registered trials
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