Revealing a Natural Model of Pre-Osteoarthritis of the Hip Through Study of Femoroacetabular Impingement

Femoroacetabular impingement (FAI) is considered the mechanical cause of hip osteoarthritis (OA). Surgical intervention involves labrum repair and osteochondroplasty to remove the impingement, alleviating symptoms. Nevertheless, some patients progress to hip OA after surgery, indicating that factors other than mechanical abnormality are contributing to hip OA progression. This review article discusses our laboratory's studies on hip FAI and OA, undertaken to identify key molecular players in the progression of hip OA. Transcriptome analysis identified peroxisome proliferator activated receptor gamma (PPAR gamma) as a crucial molecule in early hip OA. PPAR gamma, widely expressed in chondrocytes, has a protective role in preventing OA, but its true mechanism remains unknown. We observed a dysregulation of DNA methyltransferase (DNMT) in the progression of hip OA, with high expression of DNMT1 and 3A and downregulation of DNMT3B. Moreover, we established that DNMT3A is the main molecule that is binding to PPAR gamma promoter CpG area, and hypermethylation of this area occurs during disease progression. This suggests that epigenetic changes are a main mechanism that regulates PPAR gamma expression. Finally, we developed a novel rabbit model of hip FAI and OA and are currently performing studies to validate our small-animal model to human FAI.