All together, this study revealed substantial alterations in the vimentin cytoskeleton in OA-affected human articular chondrocytes.

Catabolic cytokine and anabolic growth factor pathways control destruction and repair in osteoarthritis (OA). A unidirectional TNF-alpha/IL-1-driven cytokine cascade disturbs the homeostasis of the extracellular matrix of articular cartilage in OA. Although chondrocytes in OA cartilage overexpress anabolic insulin-like growth factor (IGF) and its specific receptor (IGFRI) autocrine TNF-alpha released by apoptotic articular cartilage cells sets off an auto/paracrine IL-1-driven cascade that overrules the growth factor activities that sustain repair in degenerative joint disease. Chondroprotection with reappearance of a joint space that had disappeared has been documented unmistakably in peripheral joints of patients suffering from spondyloarthropathy when treated with TNF-alpha-blocking agents that repressed the unidirectional TNF-alpha/IL-1-driven cytokine cascade. A series of connective tissue structure-modifying agents (CTSMAs) that directly affect IL-1 synthesis and release in vitro and down-modulate downstream IL-1 features, e.g. collagenase, proteoglycanase and matrix metalloproteinase activities, the expression of inducible nitric oxide synthase, the increased release of nitric oxide, and the secretion of prostaglandin E(2), IL-6 and IL-8, have been shown to possess disease-modifying OA drug (DMOAD) activities in experimental models of OA and in human subjects with finger joint and knee OA. Examples are corticosteroids, some sulphated polysaccharides, chemically modified tetracyclines, diacetylrhein/rhein, glucosamine and avocado/soybean unsaponifiables.

Paired analysis of normal and OA chondrocytes from the same knee joint has shown an enhanced capacity of chondrocytes from OA cartilage to produce ECM macromolecules. However, the same cells have increased catabolic signalling pathways. As a consequence of this increased IL-1 activity and the reduced amounts of IL-1RII decoy receptor, less of the produced ECM macromolecules may persist in the CAM of the OA chondrocytes.

Some aspects of ECM metabolism of normal cartilage were evaluated by flow cytometry. Chondrocytes from normal human cartilage, when cultured in gelled agarose, showed correlations between the expression of TGF-betaRII/TGF-beta1 and the intracellular levels of TIMPs, indicating that TGF-beta autocrine pathway may contribute to homeostasis of the ECM in the normal cartilage. The relations between MMPs, TIMPs and the ECM molecules support that a physiological balance between MMPs and TIMPs results in a well-controlled matrix turnover in normal cartilage.

Flow cytometry offers an efficient tool to study the metabolism of the chondrocyte CAM. The MFI has been used as a parameter to quantify the ECM molecules in the CAM.