Stage-dependent Expression of Autophagy-related Genes in Patients With Knee Osteoarthritis.

BACKGROUND/AIM: Autophagy plays a crucial role in maintaining cellular homeostasis and has been implicated in the pathogenesis of knee osteoarthritis (OA). However, data on radiographic stage-dependent transcriptional variation of autophagy-related genes in patients with knee OA, particularly using peripheral blood samples, remain limited. The aim of this study was to evaluate whether disease severity was associated with stage-dependent changes in the expression of selected autophagy-related genes within a patient cohort.

PATIENTS AND

METHODS

A total of 200 patients diagnosed with knee OA were included in the study. Disease severity was classified according to the Kellgren-Lawrence radiographic grading system. Peripheral blood samples were collected, and the expression levels of selected autophagy-related genes were analyzed using quantitative real-time polymerase chain reaction [autophagy-related 5 (ATG5), ATG7, unc-51-like kinase 1 (ULK1), microtubule-associated protein 1 light chain 3 beta (LC3B), WD repeat domain phosphoinositide-interacting protein 1 (WIPI1), neighbor of BRCA1 gene 1 (NBR1), forkhead box O3 (FOXO3), transcription factor EB (TFEB)]. Relative gene expression was calculated using the ΔCt method, and comparisons were performed across radiographic stages. Associations between gene expression levels and systemic inflammatory markers were also assessed.

RESULTS

Significant stage-dependent differences were observed in the expression of ULK1, TFEB, WIPI1, and NBR1 (p<0.05), with higher ΔCt values (reduced relative expression) in advanced radiographic stages compared with early-stage disease. In contrast, ATG5, ATG7, LC3B, and FOXO3 expression remained stable across radiographic stages. Furthermore, no significant associations were observed between expression of autophagy-related genes and systemic inflammatory status, as assessed by C-reactive protein levels.

CONCLUSION

In patients with knee OA, regulatory and early autophagy-related genes exhibit radiographic stage-associated transcriptional alterations in peripheral blood, while expression of core autophagy machinery genes remain relatively stable. These findings suggest that disease severity is associated with selective transcriptional changes in autophagy-related pathways within the OA patient population and support further investigation of stage-dependent molecular patterns in knee OA.