Our lab focuses on hip osteoarthritis (OA), specifically we are interested in understanding the early molecular mechanisms in hip joint OA disease. OA is a major debilitating disease affecting 27 million persons in the US and is the leading cause of chronic disability in the US. Pathophysiologic mechanisms during OA have been primarily identified using tissues harvested from patients with end stage OA. However, it is likely that the disease-initiating molecular changes have already occurred in end-stage diseased joints. Femoroacetabular impingement (FAI) is recognized as a leading cause of degenerative arthritis in the hip and offers a unique opportunity to study molecular changes during early stage of hip OA.
Our lab focuses on two main questions. 1) What is the molecular mechanism in which hip impingement results in OA disease? Our previous study revealed that cartilage from the impingement zone in hip FAI presented an OA phenotype and with severe inflammation, This molecular inflammation may involve the mechanism by which impingement may be a structural precursor to hip OA. Our recent RNA sequence analysis identified several key genes and pathways (PPARγ, PI3K/Akt/mTOR) that may be playing a key role during early stage of FAI disease. In addition, recent advance in OA research revealed that OA progression is associated with abnormal epigenetic changes of many OA-susceptible genes. Our preliminary investigation also confirmed aberrant expressions of DNA methyltransferases (DNMTs) with advanced disease. We are currently studying the methylation status at specific gene promoter (methylation specific PCR) and the direct interaction between specific proteins and DNA methyltransferases (ChIP assay). In the future, we are planning to evaluate the chondrocyte autophagy and synovial macrophage polarizations to investigate the role that autophagy plays in FAI. The second question is: 2) Does modulation of the identified key pathways by therapeutic intervention rescue chondrocytes from the catabolic state and slow down progression of hip osteoarthritis? We are currently doing in vitro study focusing on the PPARγ pathway to investigate the impact of modulation of this pathway on the chondrocyte phenotype for early and late-stage FAI. Our group established a novel small animal model of cam-deformity by intentionally injuring the proximal femoral physis in immature hips from rabbits. We are currently performing in vivo small animal model of FAI to understand how localized inflammation at impingement areas progresses to OA in the entire joint. This model will serve as a platform to study the mechanism disease and development of disease modifying therapies.
Our goal is to contribute to the discovery of novel approaches to intervene to slow down OA progression in patients with hip disease.