Osteoarthritis is now widely accepted to be a disease of the whole joint. Hence, the clinical symptoms, pain and loss of function, can be explained by structural changes to the articular cartilage, the presence of inflammation in the synovium and the subchondral bone, subchondral and juxta-articular bone remodeling with osteophyte formation. However, it is also increasingly clear that osteoarthritis refers to a group of diseases with different pathophysiological mechanisms involved leading towards a common outcome: progressive joint failure. Osteoarthritis is the most common chronic joint disease yet an integrating concept of the pathophysiology remains largely obscure. In this context, the role of inflammation has triggered a lot of attention as many tools to target inflammation in a clinical context have been introduced for other forms of joint disease
Osteoarthritis can be considered as a ‘chronic wound’. In this model endogenous danger/damage associated molecular patterns (DAMPs) from diseased joint tissues initiate a progressive cycle of innate immune activation and contribute to tissue damage. The advances in systemic genomic, proteomic, and imaging screening technologies identified biological processes, cells, and tissues that are altered during the onset and progression of OA. In many cases, OA is characterized by the presence of low-grade inflammation, with activation of various innate immune effector cells, pathways, and molecules. However, many questions remain about how these immune responses contribute to OA pathogenesis and disease progression.
The role of inflammation, in particular in the synovium, has been extensively studied and debated. There is good evidence that synovitis contributes to the disease symptoms and that different cells of the immune system can play an active role. Innate immune not driven by antigen-specific reactions appear to be the most important, with macrophages taking front centre as cells involved. Yet, targeted strategies using biologicals have not been convincingly successful in clinical trials to prevent or retard the progression of disease, in sharp contrast to the management of diseases such as rheumatoid and spondyloarthritis. This suggests that either the factors driving inflammation have not been well identified or that direct targeting single cytokines does not cover the complexity of the disease processes.
In addition, inflammatory mediators and reaction of tissue resident stromal cells, including articular chondrocytes, also contribute to the disease and are part of the complex molecular network involved in the pathophysiology. It remains an open question whether we can currently adequately assess this type of inflammation, let alone treat it. Here alternative therapeutic approaches may be worth studying to impact the disease.
Endogenous inflammation in the chondrocytes likely contributes to the progression of disease as many studies with transcriptome analysis point towards an activated state of the chondrocytes that affects the differentiation status and extra-cellular matrix production. These progressive insights contribute to a more holistic understanding of osteoarthritis.
In this context targeting inflammation remains an attractive target for the treatment of osteoarthritis. Yet such novel treatment may require novel strategies and tools to go beyond the oft considered secondary roles of synovitis but can also target the stromal cells' response.
Academic research in the THD laboratory is supported by FWO Vlaanderen (Flanders Research Foundation), KU Leuven, the Excellence of Science initiative of the Federal Government, the EU H2020 and IMI2 program, Foreum and the VIB-Grand Challenges Program