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Arthritis

Following is another brief/adaptation from the excellent  review article from OARSI, Osteoarthritis Research Society International

Osteoarthritis as an inflammatory disease (osteoarthritis is not osteoarthrosis!)

F.Berenbaum

University Pierre & Marie Curie, Paris VI, Sorbonne Universités, 7 quai St-Bernard, 75252 Cedex 5 Paris, France

Department of Rheumatology, AP-HP Saint-Antoine Hospital, 75012 Paris, France

Osteoarthritis (OA) has long been considered a “wear and tear” disease leading to loss of cartilage. This paradigm was mainly based on the observation that chondrocytes, the only cell type present in cartilage, have very low metabolism activity with no ability to repair cartilage. Moreover, unlike all other tissues, articular cartilage, once damaged, cannot respond by a usual inflammatory response because it is non-vascularized and non-innervated.

The discovery that many soluble mediators such as cytokines or prostaglandins can increase the production of matrix metalloproteinases (MMPs) by chondrocytes led to the first steps of an “inflammatory” theory. However, it took a decade before synovitis was accepted as a critical feature of OA, and some studies are now opening the way to consider the condition a driver of the OA process.

Thus, initially considered cartilage driven, OA is a much more complex disease with inflammatory mediators released by cartilage, bone and synovium.

 

Synovitis (local inflammation) in OA

Joint swelling is one clinical feature of OA attributed to inflammation and reflecting the presence of synovitis due to thickening of the synovium or to effusion. When patients experience OA flares (night pain, morning stiffness), they usually exhibit in parallel joint effusion, as is seen in classical inflammatory arthropathies such as rheumatoid arthritis (RA).

Systemic high-sensitivity C-reactive protein levels reflect synovial inflammation in OA patients and are associated with level of pain.

Why the synovium becomes inflamed in OA remains controversial. The most accepted hypothesis is that, once degraded, cartilage fragments fall into the joint and contact the synovium. Considered foreign bodies, synovial cells react by producing inflammatory mediators, found in synovial fluid. These mediators can activate chondrocytes present in the superficial layer of carti-lage, which leads to metalloproteinase synthesis and, eventually, increase cartilage degradation. The mediators can also induce synovial angiogenesis and increase the synthesis of inflammatory cytokines and MMPs by synovial cells themselves (vicious circle). Thus, OA synovitis perpetuates the cartilage degradation.

Low-grade systemic inflammation in OA

Local production of inflammatory mediators are well known to contribute to cartilage degradation and synovial cell activation, but additional data may link these events to a more systemic pathway. In other words, inflammatory events occurring within joint tissues could be reflected outside the joint in plasma and peripheral blood leukocytes (PBLs) of patients with OA. Levels of several inflammatory mediators are higher in OA than healthy sera . A remarkable study assessed gene expression profiles in PBLs from patients with OA and found a subset with activated PBLs. Interestingly, cluster analysis revealed two distinct subgroups: one with increased level of IL-1b and one with normal expression. Patients with the inflammatory “IL-1b signature” had higher pain scores and decreased function and were at higher risk of radiographic progression of OA.

 

Moreover, systemic adipokines were found associated with local synovial tissue inflammation 52. Recently, the infrapatellar fat pad, an adipose tissue localized in the knee, was found to be a potential source of adipokines such as IL-6 5

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