Inflammation in obesity-driven osteoarthritis: Investigating the role of monocytes and macrophages

Abstract

Osteoarthritis (OA) is a joint disease that causes pain and limitations in mobility. Current treatment of OA is focused on management of symptoms and joint replacement surgery at end stage disease, and no curative or disease-modifying treatment is available. Despite large advances over the past decades, the underlying pathophysiology of OA is still partly unclear as many factors contribute to the development of OA. In addition, the large heterogeneity of the osteoarthritic patient population suggest there might be a different underlying disease etiology in different subset populations, that may need different treatment approaches. We suspect that a large subset of patients is described by the metabolic-OA phenotype, where obesity and its subsequent low-grade systemic inflammation will accelerate the development of OA locally in the joint. Two cell types that contribute tot his low grade inflammation are monocytes and macrophages. This thesis aimed to investigate the effects of obesity-induced systemic inflammation on joint inflammation and OA development. We focused on characterizing macrophage and monocyte inflammation, with the goal to find potential targets for treatment or diagnostics, as there is a great need for better treatment options and early diagnosis tools in OA.