Synovial fluid mitochondrial DNA as a biomarker after naturally occurring intra-articular fracture

2021 ◽  
Vol 29 ◽  
pp. S91-S92
Author(s):  
L.A. Seewald ◽  
I.G. Sabino ◽  
A. Bohner ◽  
M.L. Delco
Keyword(s):  
Mitochondrial Dna ◽  
Synovial Fluid ◽  
Articular Fracture ◽  
Naturally Occurring

scholarly journals Synovial Fluid Mitochondrial DNA Concentration Reflects the Degree of Cartilage Damage After Naturally Occurring Articular Injury

2021 ◽  
Author(s):  
Lindsay A Seewald ◽  
Isabella G Sabino ◽  
Kaylee L Montney ◽  
Michelle L Delco
Keyword(s):  
Mitochondrial Dna ◽  
Synovial Fluid ◽  
Cartilage Damage ◽  
Joint Surface ◽  
Therapeutic Success ◽  
Joint Injury ◽  
Naturally Occurring ◽  
Molecular Pattern ◽  
Extracellular Release ◽  
Sensitive Marker

Posttraumatic osteoarthritis (PTOA) is a debilitating sequela to joint injury with no current therapeutics that can slow its progression. Early intervention, prior to the development of degenerative joint changes, has the potential for greater therapeutic success but requires early detection of joint injury. In other tissue types, trauma is associated with the extracellular release of mitochondrial DNA (mtDNA), which serves as a mitochondria-specific Damage Associated Molecular Pattern (mDAMP) to perpetuate inflammation. We demonstrated that chondrocytes release mtDNA following cellular stress and that mtDNA is increased in equine synovial fluid following experimental and naturally occurring mechanical injury to the joint surface. Moreover, we found a strong correlation between the degree of cartilage damage and mtDNA concentration. Finally, impact-induced mtDNA release was mitigated by mitoprotective treatment. These data suggest synovial fluid mtDNA may represent a sensitive marker of early articular injury, prior to the onset of changes on standard diagnostic imaging modalities.

scholarly journals Evaluation of serum MMP-2 and MMP-3, synovial fluid IL-8, MCP-1, and KC concentrations as biomarkers of stifle osteoarthritis associated with naturally occurring cranial cruciate ligament rupture in dogs

PLoS ONE ◽  
2020 ◽  
Vol 15 (11) ◽  
pp. e0242614
Author(s):  
Sarah Malek ◽  
Hsin-Yi Weng ◽  
Shannon A. Martinson ◽  
Mark C. Rochat ◽  
Romain Béraud ◽  
...  
Keyword(s):  
Synovial Fluid ◽  
Linear Regression ◽  
Cruciate Ligament ◽  
Discriminative Ability ◽  
Cranial Cruciate Ligament ◽  
Discriminative Performance ◽  
Naturally Occurring ◽  
Veterinary Pathologist ◽  
Concentration Changes ◽  
And Control

The purpose of this study was to evaluate matrix metalloproteinases (MMP) -2 and MMP-3 in serum, and keratinocyte-derived chemoattractant (KC), interleukin 8 (IL-8) and monocyte chemoattractant 1 (MCP-1) in synovial fluid (SF) as stifle osteoarthritis (OA) biomarkers in dogs. Dogs with naturally occurring cranial cruciate ligament (CrCL) rupture (OA group) and healthy controls were recruited. Stifles with CrCL deficiency were surgically stabilized. Serum, SF, and synovial biopsy samples were collected from the OA group preoperatively, whereas samples were collected once from control dogs. A blinded veterinary pathologist graded synovial biopsies. Serum and SF analyses were performed using xMAP technology. General linear regression was used for statistical comparisons of serum biomarkers, and mixed linear regression for SF biomarkers and temporal concentration changes. The overall discriminative ability was quantified using area under curve (AUC). Spearman’s correlation coefficient was used to assess correlations between synovial histology grades and the biomarkers. Samples from 62 dogs in the OA group and 50 controls were included. The MMP-2 and MMP-3 concentrations between the OA and control groups were not significantly different, and both with an AUC indicating a poor discriminative ability. All three SF biomarker concentrations were significantly different between the OA group and controls (P <0.05). The MCP-1 was the only biomarker showing an acceptable discriminative performance with an AUC of 0.91 (95% confidence interval: 0.83–0.98). The sum of the inflammatory infiltrate score was significantly correlated with all three SF biomarkers (P <0.01). Summed synovial stroma, and all scores combined were significantly correlated with IL-8 and MCP-1 concentrations (P <0.003), and the summed synoviocyte scores were significantly correlated with MCP-1 concentrations (P <0.001). Correlations between MCP-1 concentrations and synovial histopathologic grading and its discriminative ability suggest its potential as a synovitis biomarker in canine stifle OA associated with CrCL rupture.

Evaluation of Intravenously Delivered Allogeneic Mesenchymal Stem Cells for Treatment of Elbow Osteoarthritis in Dogs: A Pilot Study

2019 ◽  
Vol 32 (03) ◽  
pp. 173-181 ◽  
Author(s):  
Anastasia Olsen ◽  
Valerie Johnson ◽  
Tracy Webb ◽  
Kelly Santangelo ◽  
Steven Dow ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Synovial Fluid ◽  
Outcome Measures ◽  
Post Treatment ◽  
Joint Fluid ◽  
Clinical Effects ◽  
Vertical Force ◽  
Naturally Occurring ◽  
Elbow Osteoarthritis

Objectives The aim of this study was to evaluate the safety and collect pilot data measuring clinical effects of intravenously administered, adipose-derived, culture-expanded, allogeneic mesenchymal stem cells in dogs with elbow osteoarthritis. Materials and Methods Dogs (n = 13) with naturally occurring elbow osteoarthritis received three intravenous doses of allogeneic canine mesenchymal stem cells via an open-label clinical trial. Primary outcome measures collected over a 6-month study period included objective gait analysis, accelerometry, owner questionnaires and joint fluid analysis. Results No acute adverse events were observed following repeated intravenous treatment with allogeneic mesenchymal stem cells. A significant improvement in mean client-specific outcome measure (CSOM) activity score and CSOM behaviour score was observed when pre-treatment values were compared with post-treatment values (day >28). In contrast, mean peak vertical force significantly decreased from baseline to post-treatment (>day 28). Weekly activity counts did not show a significant difference between baseline to post-treatment time points. Synovial fluid biomarkers did not change during treatment, and labelled mesenchymal stem cells were rarely detected in synovial fluid samples collected after mesenchymal stem cell administration. Clinical Significance For dogs with naturally occurring elbow osteoarthritis, intravenous administration of mesenchymal stem cells was clinically well tolerated. While some subjective outcome measures showed significant improvements, objective outcome measures did not confirm similar changes. Further research is needed before intravenous mesenchymal stem cells can be recommended as a treatment for elbow osteoarthritis in dogs.

Synovial fluid gelatinase concentrations and matrix metalloproteinase and cytokine expression in naturally occurring joint disease in horses

2001 ◽  
Vol 62 (9) ◽  
pp. 1467-1477 ◽  
Author(s):  
Troy N. Trumble ◽  
Gayle W. Trotter ◽  
Julie R. Thom Oxford ◽  
C. Wayne McIlwraith ◽  
Sheryl Cammarata ◽  
...  
Keyword(s):  
Synovial Fluid ◽  
Matrix Metalloproteinase ◽  
Cytokine Expression ◽  
Joint Disease ◽  
Naturally Occurring

scholarly journals Articular fracture upregulates lipid metabolites in human synovial fluid

2017 ◽  
Vol 25 ◽  
pp. S381 ◽  
Author(s):  
B.D. Furman ◽  
K.A. Kimmerling ◽  
S. Ramamoorthy ◽  
Y.-J. Li ◽  
Y.-H. Wu ◽  
...  
Keyword(s):  
Synovial Fluid ◽  
Articular Fracture ◽  
Lipid Metabolites ◽  
Human Synovial Fluid

scholarly journals Mitochondrial DNA Variation and Selfish Propagation Following Experimental Bottlenecking in Two Distantly Related Caenorhabditis briggsae Isolates

Genes ◽  
2020 ◽  
Vol 11 (1) ◽  
pp. 77 ◽  
Author(s):  
Josiah T. Wagner ◽  
Dana K. Howe ◽  
Suzanne Estes ◽  
Dee R. Denver
Keyword(s):  
Mitochondrial Dna ◽  
Copy Number ◽  
Large Deletion ◽  
Specific Pattern ◽  
Caenorhabditis Briggsae ◽  
Selfish Dna ◽  
Naturally Occurring ◽  
Animal Populations ◽  
Mtdna Evolution ◽  
Species Specific

Understanding mitochondrial DNA (mtDNA) evolution and inheritance has broad implications for animal speciation and human disease models. However, few natural models exist that can simultaneously represent mtDNA transmission bias, mutation, and copy number variation. Certain isolates of the nematode Caenorhabditis briggsae harbor large, naturally-occurring mtDNA deletions of several hundred basepairs affecting the NADH dehydrogenase subunit 5 (nduo-5) gene that can be functionally detrimental. These deletion variants can behave as selfish DNA elements under genetic drift conditions, but whether all of these large deletion variants are transmitted in the same preferential manner remains unclear. In addition, the degree to which transgenerational mtDNA evolution profiles are shared between isolates that differ in their propensity to accumulate the nduo-5 deletion is also unclear. We address these knowledge gaps by experimentally bottlenecking two isolates of C. briggsae with different nduo-5 deletion frequencies for up to 50 generations and performing total DNA sequencing to identify mtDNA variation. We observed multiple mutation profile differences and similarities between C. briggsae isolates, a potentially species-specific pattern of copy number dysregulation, and some evidence for genetic hitchhiking in the deletion-bearing isolate. Our results further support C. briggsae as a practical model for characterizing naturally-occurring mtgenome variation and contribute to the understanding of how mtgenome variation persists in animal populations and how it presents in mitochondrial disease states.

scholarly journals Naturally occurring mitochondrial DNA heteroplasmy in the MRL mouse

Mitochondrion ◽  
2008 ◽  
Vol 8 (5-6) ◽  
pp. 358-366 ◽  
Author(s):  
Paweł Sachadyn ◽  
Xiang-Ming Zhang ◽  
Lise Desquenne Clark ◽  
Robert K. Naviaux ◽  
Ellen Heber-Katz
Keyword(s):  
Mitochondrial Dna ◽  
Naturally Occurring ◽  
Mitochondrial Dna Heteroplasmy ◽  
Mrl Mouse

scholarly journals Amino Acid Profile of Synovial Fluid Following Intra-articular Ankle Fracture

2018 ◽  
Vol 39 (10) ◽  
pp. 1169-1177
Author(s):  
Elizabeth M. Leimer ◽  
Laura M. Tanenbaum ◽  
Dana L. Nettles ◽  
Richard D. Bell ◽  
Mark E. Easley ◽  
...  
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Synovial Fluid ◽  
Ankle Fracture ◽  
Amino Acid Metabolism ◽  
Acid Metabolism ◽  
Glutathione Metabolism ◽  
Articular Fracture ◽  
Matrix Metalloproteinase 1 ◽  
Acid Metabolites

Background: Post-traumatic osteoarthritis (PTOA) is a frequent complication in patients with a previous traumatic joint injury, and the pathophysiology is not well understood. The goal of this study was to characterize the biochemical signature of amino acids, peptides, and amino acid metabolites in ankle synovial fluid following intra-articular fracture. Methods: Synovial fluid from both the injured and contralateral ankles of 19 patients with an intra-articular ankle fracture was obtained and analyzed via metabolic profiling. Follow-up analysis was performed after 6 months in 7 of these patients. Results: Statistical comparisons between injured and contralateral ankles revealed that 19 of the 66 measured amino acids, peptides, and amino acid metabolites were significantly elevated at time of fracture. Metabolites associated with glutathione metabolism exhibited the most elevated mean-fold changes, indicating a possible role for oxidative stress in fractured ankles. None of the metabolites elevated at baseline were significantly elevated after 6 months, but 6 metabolites had mean-fold changes greater than 2.1 at this time point. Multiple metabolites also exhibited significant correlations ( r > 0.575) with matrix metalloproteinase-1 and -9. Conclusion: These results indicate the presence of amino acid metabolic products in the setting of ankle fracture and suggest that these changes in amino acid metabolism may be chronic and indicate a role for inflammation and collagen degradation in disease progression. Clinical Relevance: Changes in amino acid metabolism following intra-articular fracture may contribute to the progression to PTOA. This knowledge may allow for the identification and early treatment of patients at risk of developing PTOA. Level of Evidence: Level III, comparative series.

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