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

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.

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.

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.

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.