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Osteoarthritis and cartilage2023; 31(8); 1056-1065; doi: 10.1016/j.joca.2023.03.013

Synovial fluid mitochondrial DNA concentration reflects the degree of cartilage damage after naturally occurring articular injury.

Abstract: To evaluate mitochondrial DNA (mtDNA) release from injured chondrocytes and investigate the utility of synovial fluid mtDNA concentration in early detection of posttraumatic osteoarthritis. We measured mtDNA release using four models of osteoarthritis: in vitro interleukin-1β stimulation of cultured equine chondrocytes, ex vivo mechanical impact of bovine cartilage explants, in vivo mechanical impact of equine articular cartilage, and naturally occurring equine intraarticular fracture. In our in vivo model, one group was treated with an intraarticular injection of the mitoprotective peptide SS-31 following cartilage injury. mtDNA content was quantified using qPCR. For naturally occurring cases of joint injury, clinical data (radiographs, arthroscopic video footage) were scored for criteria associated with degenerative joint disease. Chondrocytes released mtDNA in the acute time frame following inflammatory and mechanical cellular stress in vitro. mtDNA was increased in equine synovial fluid following experimental and naturally occurring injury to the joint surface. In naturally occurring posttraumatic osteoarthritis, we found a strong positive correlation between the degree of cartilage damage and mtDNA concentration (r = 0.80, P = 0.0001). Finally, impact-induced mtDNA release was mitigated by mitoprotective treatment. Changes in synovial fluid mtDNA occur following joint injury and correlate with the severity of cartilage damage. Mitoprotection mitigates increases in synovial fluid mtDNA suggesting that mtDNA release may reflect mitochondrial dysfunction. Further investigation of mtDNA as a potentially sensitive marker of early articular injury and response to mitoprotective therapy is warranted.
Copyright © 2023 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.
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Publication Date: 2023-04-06 PubMed ID: 37028640PubMed Central: PMC10524327DOI: 10.1016/j.joca.2023.03.013Google Scholar: Lookup
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  • Non-U.S. Gov't

Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

The research article investigates the potential of using mitochondrial DNA released from injured cartilage cells as an early detection marker for posttraumatic osteoarthritis. The research found a significant correlation between the level of cartilage damage and the concentration of this DNA in the synovial fluid that lubricates joints.

Objective and Methodology

  • The goal of the research was to evaluate the release of mitochondrial DNA (mtDNA) from injured so-called chondrocytes (cartilage cells), and explore the possibility of using this DNA as an early detection biomarker for posttraumatic osteoarthritis.
  • The release of mitochondrial DNA was measured using four models of osteoarthritis: cultured equine chondrocytes stimulated with interleukin-1β, mechanically impacted bovine cartilage, mechanically impacted equine articular cartilage, and equine intraarticular fracture.
  • For the in vivo model, one group was treated with SS-31, a mitoprotective peptide, after cartilage injury to assess its impact on DNA release.
  • Mitochondrial DNA was quantified using quantitative PCR (qPCR). For natural joint injury cases, clinical data like radiographs and arthroscopic video footage were scored for degenerative joint disease criteria.

Findings and Implications

  • The study found that chondrocytes released mtDNA following inflammatory and mechanical stress.
  • The concentration of mtDNA was found to increase in the synovial fluid following experimental and naturally occurring joint injury.
  • The researchers discovered a strong correlation (r = 0.80, p = 0.0001) between cartilage damage scales and mtDNA concentration for naturally occurring posttraumatic osteoarthritis cases. This indicates that the more severe the cartilage damage, the higher the concentration of mtDNA.
  • The inclusion of a mitoprotective treatment showed that it was possible to mitigate the release of mtDNA post-impact, suggesting that mtDNA release could be linked to mitochondrial dysfunction.
  • Overall, the results suggest that changes in synovial fluid mtDNA are indicative of joint injury severity and hence, mtDNA could be a potentially sensitive marker for early detection of articular injury.
  • The findings also open up avenues for further investigation into the potential of mitoprotective therapy in managing osteoarthritis, especially in mitigating posttraumatic mtDNA release.

Cite This Article

APA
Seewald LA, Sabino IG, Montney KL, Delco ML. (2023). Synovial fluid mitochondrial DNA concentration reflects the degree of cartilage damage after naturally occurring articular injury. Osteoarthritis Cartilage, 31(8), 1056-1065. https://doi.org/10.1016/j.joca.2023.03.013

Publication

Osteoarthritis and cartilage
ISSN: 1522-9653
NlmUniqueID: 9305697
Country: England
Language: English
Volume: 31
Issue: 8
Pages: 1056-1065

Researcher Affiliations

Seewald, L A
  • College of Veterinary Medicine, Cornell University, Ithaca, NY, USA. Electronic address: las498@cornell.edu.
Sabino, I G
  • College of Veterinary Medicine, Cornell University, Ithaca, NY, USA. Electronic address: igs26@cornell.edu.
Montney, K L
  • College of Veterinary Medicine, Cornell University, Ithaca, NY, USA. Electronic address: km884@cornell.edu.
Delco, M L
  • College of Veterinary Medicine, Cornell University, Ithaca, NY, USA. Electronic address: mld12@cornell.edu.

MeSH Terms

  • Animals
  • Horses
  • Cattle
  • Synovial Fluid / chemistry
  • DNA, Mitochondrial / metabolism
  • Cartilage, Articular / metabolism
  • Mitochondria
  • Osteoarthritis / metabolism
  • Joint Diseases
  • Chondrocytes

Grant Funding

  • K08 AR068470 / NIAMS NIH HHS
  • R03 AR075929 / NIAMS NIH HHS

Conflict of Interest Statement

Conflict of interest: The authors declare no competing interests.

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Citations

This article has been cited 6 times.
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