The Role of Alarmins in Osteoarthritis Pathogenesis: HMGB1, S100B and IL-33

Osteoarthritis (OA) is a multifactorial disease in which genetics, aging, obesity, and trauma are well-known risk factors. It is the most prevalent joint disease and the largest disability problem worldwide. Recent findings have described the role of damage-associated molecular patterns (DAMPs) in the course of the disease. In particular, alarmins such as HMGB1, IL-33, and S100B, appear implicated in enhancing articular inflammation and favouring a catabolic switch in OA chondrocytes. The aims of this review are to clarify the molecular signalling of these three molecules in OA pathogenesis, to identify their possible use as staging biomarkers, and, most importantly, to find out whether they could be possible therapeutic targets. Osteoarthritic cartilage expresses increased levels of all three alarmins. HMGB1, in particular, is the most studied alarmin with increased levels in cartilage, synovium, and synovial fluid of OA patients. High levels of HMGB1 in synovial fluid of OA joints are positively correlated with radiological and clinical severity. Counteracting HMGB1 strategies have revealed improving results in articular cells from OA patients and in OA animal models. Therefore, drugs against this alarmin, such as anti-HMGB1 antibodies, could be new treatment possibilities that can modify the disease course since available medications only alleviate symptoms.

Automated summary

Osteoarthritis (OA) is a prevalent and disabling joint disease influenced by various factors. Recent research has revealed the involvement of damage-associated molecular patterns (DAMPs), particularly alarmins like HMGB1, IL-33, and S100B, in promoting inflammation and degradation in OA chondrocytes. Identifying the molecular signaling of these molecules, their potential use as biomarkers for disease staging, and their suitability as therapeutic targets are important objectives. High levels of HMGB1, in particular, have been observed in OA cartilage, synovium, and synovial fluid, and are associated with disease severity. Strategies targeting HMGB1 have shown promising results in OA cells and animal models and could provide new treatment options for modifying disease progression.