Arthritis Research & Therapy最新文献

Background: Systemic lupus erythematosus (SLE) is an incurable chronic autoimmune disease of unknown etiology. Therefore, the development of new treatments is urgently needed. This study aimed to investigate the therapeutic effects of extracellular vesicles (EV) derived from immortalized mesenchymal stem cells (iMSCs) primed with conditioned media obtained from disease-conditioned immune cells (CM-EV) and iMSC-derived EV (ASC-EV) in a murine model of SLE.

Methods: Female NZB/W F1 mice were divided into the control (C, n = 15), ASC-EV (E, n = 15), and CM-EV (CM, n = 15) groups. Mice in the C, E, and CM groups were intravenously administered saline, ASC-EV, and CM-EV, respectively, once weekly from 6 to 42 weeks of age.

Results: Compared to the ASC-EV, the CM-EV showed a significant increase in TGF-β1 production and miR-155-5p and miR-142-3p expression. CM-EV treatment increased survival, decreased anti-dsDNA antibody levels, and ameliorated renal histopathology. Although ASC-EV treatment significantly reduced the incidence of severe proteinuria and improved renal histopathology, it did not significantly improve survival rate. ASC-EV or CM-EV treatment significantly decreased the proportion of pro-inflammatory macrophages (CD11c + CD206-; M1) and M1:M2 ratio. Additionally, CM-EV treatment significantly increased the expression of anti-inflammatory macrophages (CD11c-CD206 + ; M2). Moreover, CM-EV treatment significantly decreased the expression of lupus-specific miRNAs (miR-182-5p and miR-183-5p) in the spleen.

Conclusions: EV derived from iMSCs primed with conditioned media obtained from disease-conditioned immune cells exert immunomodulatory effects and ameliorate SLE in a murine model.

Background: This study aims to develop a hierarchical classification method to automatically assess the severity of knee osteoarthritis (KOA).

Methods: This retrospective study recruited 4074 patients. Clinical diagnostic indicators and clinical diagnostic processes were applied to develop a hierarchical classification method that involved four sub-task classifications. These four sub-task classifications were the classification of Kellgren-Lawrence (KL) grade 0-2 and KL grade 3-4, KL grade 3 and KL grade 4, KL grade 0 and KL grade 1-2, and KL grade 1 and KL grade 2, respectively. To extract the features of clinical diagnostic indicators, four U-Net models were first used to segment the total joint space (TJS), the lateral joint space (LJS), the medial joint space (MJS), and osteophytes, respectively. Based on the segmentation result of TJS, the region of knee subchondral bone was generated. Then, geometric features were extracted based on segmentation results of the LJS, MJS, TJS, and osteophytes, while radiomic features were extracted from the knee subchondral bone. Finally, the geometric features, radiomic features, and combination of geometric features and radiomic features were used to construct the geometric model, radiomic model, and combined model in KL grading, respectively. A strict decision strategy was used to evaluate the performance of the hierarchical classification method in all X-ray images of testing cohort.

Results: The U-Net models achieved relatively satisfying performances in the segmentation of the TJS, the LJS, the MJS, and the osteophytes with the dice similarity coefficient of 0.88, 0.86, 0.88, and 0.64 respectively. The combined models achieved the best performance in KL grading. The accuracy of combined models was 98.50%, 81.65%, 82.07%, and 74.10% in the classification of KL grade 0-2 and KL grade 3-4, KL grade 3 and KL grade 4, KL grade 0 and KL grade 1-2, and KL grade 1 and KL grade 2, respectively. For all X-ray images of the testing cohort, the accuracy of the hierarchical classification method was 65.98%.

Conclusion: The hierarchical classification method developed in the current study is a feasible approach to assess the severity of KOA.

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.