Poster 124. Cartilage Autophagy Dysregulation during OA Progression in Hip Femoroacetabular Impingement
Year: 2026
Type: article
Abstract: Objective: Femoroacetabular impingement (FAI) is a common cause of hip pain and dysfunction in young, active individuals and is recognized as a leading cause of hip osteoarthritis (OA). Early intervention is critical to preserve joint health and prolong athletic participation. Peroxisome proliferator-activated receptor gamma (PPARγ) is reported to have a protective effect on articular cartilage. Autophagy is essential for maintaining cellular homeostasis. We have previously observed suppression of PPARγ expression and dysregulation of autophagy markers with the progression of human hip OA. This study aims to investigate the effect of PPARγ on autophagy in hip articular cartilage in human tissue. Methods: Full-thickness cartilage explants were collected from the femoral head-neck junction of patients with hip FAI who underwent hip arthroscopy for the treatment of hip cam-FAI (FAI group) and patients with end-stage FAI-related OA (OA group) who underwent total hip replacement (THR). As a non-disease (ND) group, healthy samples were procured from fresh allografts. Explants were cultured under baseline conditions, with catabolic stimulation using interleukin-1β (IL1β), or with IL1β in combination with a PPARγ agonist (Rosiglitazone) or inhibitor (T0070907). Histological analysis with safranin O and fast green (Mankin score), immunofluorescence for autophagy markers (LC3B and p62), and qPCR for LC3B, p62, and MMP-13 were performed. The comparisons between groups were performed using ANOVA, with Šídák's correction applied for multiple post hoc comparisons as appropriate. Differences were considered significant at p < 0.05 (corrected). Data expressed as mean ± SD for parametric test. Human cartilage specimens were obtained with approval from the Institutional Review Board (IRB) of Washington University School of Medicine, in accordance with the Declaration of Helsinki and relevant national regulations. Written informed consent was obtained from all patients prior to sample collection. Cartilage samples were collected from a total of 21 patients (7 with cam-type FAI, 7 with end-stage FAI-related OA, and 7 non-disease donors). Results: Cartilage degeneration was observed with an increased Mankin score following IL1β stimulation and treatment with PPARγ inhibitor (control vs. IL1β, p<0.001, control vs. PPARγ inhibitor, p=0.01) (Fig.1a). Conversely, catabolism was reduced when the cartilage was treated with a PPARγ agonist (control vs PPARγ agonist, p=0.03, Fig.1b). Imunofluorescence showed an increase in LC3B-positive cells following PPARγ agonist treatment (control vs. PPARγ agonist, ND, p=0.0428, OA, p=0.0431), while IL1β and PPARγ inhibitor reduced LC3B-positive cells (control vs. IL1β, ND, p=0.0017, OA, p=0.0028, control vs. PPARγ inhibitor, ND, p=0.0004, OA, p=0.0992, Fig.2a,b). Similarly, the number of p62-positive cells were redeced by PPARγ agonist (control vs. PPARγ agonist, ND, p=0.0109, OA, p=0.0015), while IL1β and PPARγ inhibitor increased p62-positive cells (control vs. IL1β, ND, p<0.0001, OA, p=0.0127, control vs. PPARγ inhibitor, ND, p=0.0027, OA, p<0.0001, Fig.2c,d). qPCR showed MMP-13 expression was significantly decreased with PPARγ agonist treatment (control vs. PPARγ agonist, ND, p=0.014, OA, p=0.001) and increased following IL1β stimulation and PPARγ inhibition (control vs. IL1β, ND, p=0.048, OA, p=0.011, control vs. PPARγ inhibitor, ND, p=0.002, OA, p=0.045). Co-treatment with PPARγ agonist suppressed the IL1β-induced upregulation of MMP-13 (IL1β vs. IL1β+PPARγ agonist, ND, p=0.003, FAI, p=0.016, OA, p=0.033), whereas the addition of PPARγ inhibitor reversed this effect (IL1β+PPARγ agonist vs. IL1β+PPARγ agonist+PPARγ inhibitor, ND, p=0.031, FAI, p=0.016, OA, p=0.004, Figure 3a). In parallel, LC3B expression was significantly increased after PPARγ agonist treatment (control vs. PPARγ agonist, ND, p=0.049, OA, p=0.024) and decreased following IL1β stimulation and PPARγ inhibition (control vs. IL1β, ND, p<0.001, OA, p=0.044, control vs. PPARγ inhibitor, ND, p=0.006, OA, p=0.008, Figure 3b). The IL1β-induced suppression of LC3B was rescued by PPARγ agonist (IL1β vs. IL1β+PPARγ agonist, ND, p=0.049, OA, p=0.05). p62 expression showed the opposite trend, decreased with PPARγ agonist and increased with IL1β or PPARγ inhibitor. The rescue effect was also confirmed in p62 expression following PPARγ agonist treatment (IL1β vs. IL1β+PPARγ agonist, ND, p=0.043, OA, p=0.027, Figure 3c). Conclusions: This study demonstrates that PPARγ receptor activation in human hip cartilage suppresses catabolic activity and promotes autophagy-related gene expression. PPARγ agonist treatment reduced MMP-13 levels and reversed IL1β-induced catabolic changes. These findings suggest that PPARγ plays a chondroprotective role in FAI-related cartilage degeneration. For young, active patients and athletes with FAI, targeting the PPARγ-autophagy pathway may help preserve cartilage integrity, delay OA onset, and prolong athletic participation. While this ex vivo explant model does not fully replicate the in vivo joint environment, these results support further translational and clinical studies to evaluate PPARγ modulation as a therapeutic adjunct in the management of sport-related hip injuries.
Language: English
Subfield: Rheumatology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $1,500
OpenAlex ID: W7204776305
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