Poster 112: Epigenetic Dysregulation during the OA Progression in Hip FAI

Objectives: Femoroacetabular impingement (FAI) is considered a leading cause of early hip OA, but initial molecular mechanisms that lead FAI patients to OA progression remains be elucidated. Recent articles revealed epigenetic changes are associated with progression, specifically, DNA methyltransferase 3B (DNMT3B) plays critical role on cartilage homeostasis by attenuating catabolic gene expression. This study aimed examine the state articular chondrocyte (ACs) during in disease, particularly expressions DNMT3B and 4-aminobutyrate aminotransferase (ABAT, downstream DNMT3B), assess how dysregulation contributes progression. Methods: Full-thickness samples were collected from zone. In total, twelve underwent preservation surgery for cam (early-FAI) total replacement advanced secondary (late FAI-OA) included this study. As non-disease (ND) group, five healthy procured joint cadavers. The explants cultured unstimulated conditions or stimulus (IL1β). Histological analyses was performed safranin-O/fast-green. Gene expression analyzed via qPCR GAPDH, DNMT3B, ABAT, MMP-13, COL10A1. Protein western blotting analysis ABAT. Methylation specific PCR methylation status at ABAT promoter (epigenetic change). Results: group younger subjects lower Tönnis grade than late group; however, there no significant differences gender, BMI, α-angle between groups. Cartilage early-FAI FAI-OA showed histological phenotype (Figure 1A). RT-PCR confirmed increased MMP-13 COL10A1 1B), confirming degeneration, catabolism, hypertrophy when compared ND group. Interestingly, gradually declined as disease progressed (ND vs p<0.001, p=0.016), while p=0.035, Figure 1B). IF staining abundantly expressed chondrocytes normal decreased contrary 1C). These results supported protein 1D). MSP analysis, human characterized typical CpG island 2A, blue area). Additionally, hypomethylation end stage p=0.022, p=0.042) 2B). Catabolic IL1β FAI-OA, accentuated (early FAI: nontreatment p=0.056, FAI-OA: p=0.015, 2C) resulted further overexpression markers 3A-C). findings western-blotting 3D). Conclusions: present study, similar FAI, levels marker increased, suggesting less disease. hypo-methylation (epigenetically dysregulation) progresses. Notably, current inflammatory reduced concomitant excessive increase ACs. suggests, first time, degeneration zone progressive level may controlled part an dysregulation. Understanding mechanism will potentially provide interventional treatment pre-OA