Synovial inflammation in osteoarthritis progression

Abstract

Osteoarthritis (OA) is a progressive degenerative disease resulting in joint deterioration. Synovial inflammation is present in the OA joint and has been associated with radiographic and pain progression. Several OA risk factors, including ageing, obesity, trauma and mechanical loading, play a role in OA pathogenesis, likely by modifying synovial biology. In addition, other factors, such as mitochondrial dysfunction, damage-associated molecular patterns, cytokines, metabolites and crystals in the synovium, activate synovial cells and mediate synovial inflammation. An understanding of the activated pathways that are involved in OA-related synovial inflammation could form the basis for the stratification of patients and the development of novel therapeutics. This Review focuses on the biology of the OA synovium, how the cells residing in or recruited to the synovium interact with each other, how they become activated, how they contribute to OA progression and their interplay with other joint structures. This Review examines the biology of synovial inflammation, the cell types involved, their interactions and the role of synovitis in the development and progression of osteoarthritis. Imaging studies suggest that synovial inflammation may be present in both early osteoarthritis (OA) and advanced-stage OA and is involved in the development and progression of OA. Synovial cells coordinate the production of molecules that initiate and maintain synovial inflammation and contribute to cartilage damage during OA progression. Diverse stimuli, including bioactive lipids, prostaglandins, tricarboxylic acid cycle intermediates, cytokines and damage-associated molecular patterns, as well as clinical factors such as obesity, ageing, trauma and excessive mechanical loading, regulate the production of pro-inflammatory and anti-inflammatory mediators by synovial cells. There is a need for functional imaging and cellular and molecular studies, together with a more robust histological interpretation at different stages of OA, to better stratify patients with OA and understand the role of synovitis in OA onset and progression. Imaging studies suggest that synovial inflammation may be present in both early osteoarthritis (OA) and advanced-stage OA and is involved in the development and progression of OA. Synovial cells coordinate the production of molecules that initiate and maintain synovial inflammation and contribute to cartilage damage during OA progression. Diverse stimuli, including bioactive lipids, prostaglandins, tricarboxylic acid cycle intermediates, cytokines and damage-associated molecular patterns, as well as clinical factors such as obesity, ageing, trauma and excessive mechanical loading, regulate the production of pro-inflammatory and anti-inflammatory mediators by synovial cells. There is a need for functional imaging and cellular and molecular studies, together with a more robust histological interpretation at different stages of OA, to better stratify patients with OA and understand the role of synovitis in OA onset and progression.