Danger signals and inflammaging in osteoarthritis (Équipe Berenbaum)

Clin Exp Rheumatol. 2019;37 Suppl 120(5):48-56

Osteoarthritis (OA) is the most com- mon age-related chronic and disabling joint disease. Long considered to be a “wear and tear” disease, OA is now seen as a low-grade inflammation dis- ease that affects all tissues of the joint, involving cartilage degradation, bone remodelling, osteophytes, and synovi- tis. The process, called inflammaging, is characterised by the association of low-grade inflammation, profound changes in intra-cellular mechanisms, and the decreased efficiency of the im- mune system with ageing. The activation of innate immunity plays a critical role in the development and progression of OA. Innate immunity, including inflam- masome activation, is triggered by small endogenous molecules called alarmins or damage-associated molecular pat- terns (DAMPs). These molecules are released in the extracellular media after cell stress or damage, bind to pathogen- recognition receptors (PRRs), such as Toll-like receptors (TLRs) and the re- ceptor for advanced glycation end prod- ucts (RAGE), and activate the secretion of pro-inflammatory factors, leading to joint inflammation. Moreover, such sterile inflammation triggers cell senes- cence, characterised by a senescence- associated secretory phenotype (SASP). Understanding the substantial age-re- lated changes of joint tissues that influ- ence the pathogenesis of OA is critical to improving the quality of life of elderly people in the context of increased life expectancy. This review will focus on age-related sterile inflammation in OA and highlight the various innovative and promising therapies targeting the mechanisms of aging.