Otto Aufranc Award: Identification of Key Molecular Players in the Progression of Hip Osteoarthritis Through Transcriptomes and Epigenetics

Background: This study aimed: ( 1) to compare the transcriptome profile of articular cartilage in cam-FAI (early stage) to advanced OA secondary to cam-FAI (late stage) and (2) to investigate epigenetic changes through the expression of DNA methylation enzymes DNMT3B, DNMT1, and DNMT3A and peroxisome proliferator-activated receptor gamma (PPAR gamma) in human cartilage samples during the progression of hip OA. Methods: Full-thickness cartilage samples were collected from the anterolateral head-neck junction (impingement zone) of 22 patients (9 early-FAI and 13 late-FAI). RNA sequencing and in vitro cartilage cultures with histological analysis and immunohistochemistry staining for PPAR gamma and DNMT3B were performed. Target gene validation was confirmed with RT-PCR. Results: Fifty genes and 42 pathways were identified differentially between early and late-FAI (fold change <-1.5 or >1.5, P <.01). PPAR gamma and DNMT3B were gradually suppressed with disease progression. Contrarily, disease progression induced expression of DNMT1/3A. Conclusion: By comparing comprehensive gene expression in early and late stage hip degeneration at the whole-genome level, distinct transcriptome profiles for early and late stage disease were identified along with key molecular contributors to the progression of hip OA. Preservation of endogenous PPARg may have therapeutic potential to delay or prevent hip OA. (C) 2022 Elsevier Inc. All rights reserved.

Automated summary

This study compared the transcriptome profile of articular cartilage in early stage hip impingement to advanced hip osteoarthritis (OA) secondary to impingement, and investigated the expression of DNA methylation enzymes and peroxisome proliferator-activated receptor gamma (PPAR gamma) during hip OA progression. The study identified distinct transcriptome profiles and key molecular contributors to the progression of hip OA. Preserving endogenous PPAR gamma may have therapeutic potential for delaying or preventing hip OA.