Inflammation of the Infrapatellar Fat Pad and Knee Osteoarthritis: Investigating the associations with other joint pathologies and pain

Abstract

Osteoarthritis (OA) is a complex disease that involves mechanical, metabolic and inflammatory insults to its development. Obesity, one of the primary risk factors for OA, impacts all three of these mechanisms in disease development. In particular, the role of adipose tissue as an inflammatory organ, the involvement of adipose associated inflammation in OA and the proximity of the infrapatellar fat pad (IFP) to the synovial knee joint have driven research in recent years. This thesis aimed to investigate the role of the IFP in knee OA with the surrounding structures and clinical manifestations of the disease. In Chapter 2, I systematically appraised the current literature to evaluate the relationship between IFP associated inflammation and pain in preclinical animal and human clinical studies. A series of investigations evaluating the relationship between the IFP, surrounding joint tissues and pain in murine models are described and presented in chapter 3-5. Chapter 4 identified strong correlations between IFP adiposity, synovitis and sub-synovial fibrosis but no associations to pain. Chapter 5 built on that research by further evaluating the association of IFP adiposity and sub-synovial fibrosis to pathology in surrounding structures such as the cartilage, bone and meniscus. The subsequent chapter builds on these animal model findings to evaluate the IFP in humans. Chapter 6 showed increasing IFP(Hoffa)-synovitis was weakly correlated with lowering centripetal adiposity and serum markers of synovitis but not pain. The disassociation to pain was in stark contrast to the current literature and the findings of our systematic review. Finally, Chapter 7 presents the protocol of a proposed observational study to investigate the impact of IFP inflammation on clinical outcomes in an end-stage knee OA population and reports the feasibility of the study. This thesis provides novel insights into the relationship of IFP adiposity and inflammation to the surrounding tissue structures and pain. The findings may help direct future research to 1) validate the associations identified in the preclinical studies of this thesis, 2) further understand the relationship of the IFP to other clinical manifestations including physical function, and 3) to determine if the IFP can be a potential therapeutic target.