Correlation between circulating cell-free mitochondrial DNA content and severity of knee degeneration in patients
Yan-Lin Wu1,2, Shao-Gui Wan1, Yi Long2
1Gannan Medical University, Ganzhou City, 341000, Jiangxi Province, China.
Background:
Knee osteoarthritis (KOA) is characterized by mitochondrial damage and increased inflammation. Circulating cell-free mitochondrial DNA (ccf-mtDNA), which originates from damaged mitochondria, is an endogenous damage-associated molecular pattern (DAMPs) molecule that may trigger inflammation and is recognized as a potential biomarker for various diseases. In this study, we investigated the potential association between plasma ccf-mtDNA content and its use as a diagnostic biomarker in patients with KOA.
Methods:
We collected plasma samples from patients with KOA and healthy controls (HC). Subsequently, quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect ccf-mtDNA content in the plasma samples. We used the Kellgren-Lawrence (K-L) classification criteria to classify patients with KOA into four grades: I-IV. Disease severity in patients with KOA was assessed using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). Next, Spearman analysis was performed to observe the correlation between ccf-mtDNA content and the K-L classification and WOMAC score. Logistic regression analysis was used to evaluate the relationship between ccf-mtDNA and KOA risk.
Results:
In total, we enrolled 60 patients with KOA and HC who were matched for age, sex, and body mass index (BMI). We found that plasma ccf-mtDNA contents were significantly higher in patients with KOA (median, 2.44; quartile range, 1.10-3.79) than in HC (median, 1.08; quartile range, 0.52-2.12) (P < 0.0001). Plasma ccf-mtDNA content sequentially increased following the KOA class I-IV group (P = 0.040) and positively correlated with the K-L classification (r = 0.369, P = 0.004) and WOMAC scores (r = 0.343, P = 0.007). The ccf-mtDNA content did not significantly differ between patients with bilateral and those with single KOA (P = 0.083). Patients with high levels of ccf-mtDNA had a significantly increased risk of KOA compared with those with low levels of ccf-mtDNA (odds ratio [OR], 4.15, 95% confidence interval [CI], 1.71-10.07; P = 0.002). Quartile analysis revealed a significant dose-dependent association (P trend < 0.001).
Conclusion:
Our study's findings showed that plasma ccf-mtDNA was highly expressed in patients with KOA compared with HC. Furthermore, ccf-mtDNA content is significantly associated with the severity and risk of KOA. Therefore, its detection may provide insight into the prevention and treatment of KOA.
Insights
Plasma cell-free mitochondrial DNA (ccf-mtDNA) is significantly elevated in knee osteoarthritis (KOA) patients, correlating with disease severity and increased KOA risk. This finding suggests ccf-mtDNA may serve as a valuable biomarker for KOA.
Area of Science:
- Biochemistry
- Molecular Biology
- Immunology
Background:
- Knee osteoarthritis (KOA) involves mitochondrial damage and inflammation.
- Circulating cell-free mitochondrial DNA (ccf-mtDNA) is a damage-associated molecular pattern (DAMPs) linked to inflammation and disease.
- ccf-mtDNA is explored as a potential biomarker for various conditions.
Purpose of the Study:
- To investigate the association between plasma ccf-mtDNA levels and KOA.
- To evaluate the potential of plasma ccf-mtDNA as a diagnostic biomarker for KOA.
Main Methods:
- Plasma samples were collected from KOA patients and healthy controls (HC).
- Quantitative real-time polymerase chain reaction (qRT-PCR) measured ccf-mtDNA content.
- Kellgren-Lawrence (K-L) classification and WOMAC scores assessed KOA severity.
- Spearman and logistic regression analyses examined correlations and risk.
Main Results:
- Plasma ccf-mtDNA was significantly higher in KOA patients than in HC (P < 0.0001).
- ccf-mtDNA levels increased with KOA severity (K-L grades I-IV, P = 0.040) and correlated with K-L (r=0.369, P=0.004) and WOMAC scores (r=0.343, P=0.007).
- High ccf-mtDNA levels were associated with increased KOA risk (OR=4.15, P=0.002) in a dose-dependent manner.
Conclusions:
- Plasma ccf-mtDNA is highly expressed in KOA patients compared to HC.
- ccf-mtDNA content is significantly associated with KOA severity and risk.
- ccf-mtDNA detection may offer insights for KOA prevention and treatment.
