Inflammation in osteoarthritis: is it time to dampen the alarm(in) in this debilitating disease?

• Published in: Clinical and experimental immunology Vol. 195; no. 2; pp. 153 - 166
• Main Author: van den Bosch, M. H. J.
• Format: Journal Article
• Language: English
• Published: England Oxford University Press 01.02.2019; John Wiley and Sons Inc
• Subjects: alarmins; Alarmins - metabolism; Arthritis; Cartilage diseases; Cellular stress response; Humans; Immune system; Inflammation; Inflammation - pathology; Inflammatory diseases; Inflammatory response; Osteoarthritis; Osteoarthritis - immunology; Osteoarthritis - pathology; Osteoarthritis - therapy; Pathogenesis; pathology; Quality of life; Review; S100A8/A9; Synovial Fluid - metabolism; Synovial Membrane - pathology; Synovium; S100A8/A9; pathology; inflammation; osteoarthritis; alarmins
• ISSN: 0009-9104; 1365-2249
• DOI: 10.1111/cei.13237

Summary Osteoarthritis (OA) is the most common joint disease that strongly reduces the quality of life in patients; However, no disease‐modifying therapy is available. For a long time, OA was considered a non‐inflammatory disease that was the result of ‘wear‐and‐tear’ and abnormal mechanics, and therefore many considered the term ‘osteoarthritis’ a misnomer. However, during the last decades the notion arose that inflammation is not only present in the majority of OA patients but, rather, actively involved in the progression of the disease. Influx of immune cells is observed in the synovium and a plethora of inflammatory mediators is present in tissues and fluids from OA patients. These mediators cause the production of degrading enzymes that break down the cartilage matrix, which is the main hallmark of OA. Alarmins, which belong to the group of danger signals, have been implicated in many inflammatory diseases. They are among the first factors to be released upon cell stress due to, for example, infection, damage and inflammation. They attract and activate cells of the immune system and therefore lie at the base of the inflammatory reaction. In this narrative review, an overview of the history of OA, the evolving concept of inflammation as important factor in the OA pathogenesis, and particularly the central role that alarmins play in the initiation and maintenance of the low‐grade inflammatory response in OA, is provided. Moreover, the targeting of alarmins as a promising approach to dampen the inflammation in OA is highlighted. Whereas osteoarthritis was historically considered a disease solely of the articular cartilage, it is nowadays broadly accepted that inflammation plays a crucial role in the disease development. Of particular interest in the inflammatory cascade during osteoarthritis are the alarmins, which are released upon cell stress and lie at the basis of the immune reaction. This review gives an overview of the inflammatory processes that are involved in osteoarthritis, with a particular focus on alarmins, and provides possibilities to inhibit these alarmins.