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

Abstract

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.

Ondansetron or beta-sitosterol antagonizes inflammatory responses in liver, kidney, lung and heart tissues of irradiated arthritic rats model

“…In particular, HMGB1 interacts with TLR4, inducing cytokine production and inflammation. 69 HMGB1-stimulated peripheral blood monocytes release TNF-α, IL-10 and IL-6. 70 Supporting to our finding of increasing levels of HMGB, HMGB1 had been implicated in many inflammatory responses and autoimmunity, 71 where it could induce innate immune activation and inflammation amplification through its interactions with multiple receptors, including Toll-like receptors (TLR2 and TLR4) .…”