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!)
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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