Molecular aspects of pathogenesis in osteoarthritis: the role of inflammation

Abstract

Arthritic diseases cause enormous burdens in terms of pain, crippling, and disability. Osteoarthritis (OA), the most common form of arthritis, is characterized by a slow progressive degeneration of articular cartilage. The exact etiology of OA is not known, but the degradation of cartilage matrix components is generally agreed to be due to an increased synthesis and activation of extracellular proteinases, mainly matrix metalloproteinases. Insufficient synthesis of new matrix macromolecules is also thought to be involved, possibly as a consequence of deficient stimulation by growth factors. Although OA is defined as a noninflammatory arthropathy, proinflammatory cytokines such as interleukin-1 have been implicated as important mediators in the disease. In response to interleukin-1, chondrocytes upregulate the production of nitric oxide and prostaglandin E2, two factors that have been shown to induce a number of the cellular changes associated with OA. The generation of these key signal molecules depends on inducible enzymes and can be suppressed by pharmacological inhibitors.

Concomitant Recruitment of ERK1/2 and p38 MAPK Signalling Pathway Is Required for Activation of Cytoplasmic Phospholipase A2via ATP in Articular Chondrocytes

“…Healthy cartilage is maintained in a state of dynamic equilibrium by matrix synthesis and matrix degradation by the chondrocytes. Any dysregulation with increased degradation and/or inadequate synthesis leads to loss of tissue structure and function, as in rheumatoid arthritis (RA) 1 and osteoarthritis (OA). The proinflammatory cytokines interleukin-1␤ (IL-1␤) and tumor necrosis factor ␣ (TNF-␣) are implicated in this phenomenon.…”

“…The proinflammatory cytokines interleukin-1␤ (IL-1␤) and tumor necrosis factor ␣ (TNF-␣) are implicated in this phenomenon. They act on chondrocytes to increase the production of the major cartilage-degrading proteinases, the matrix metalloproteinases, by inhibiting the synthesis of cartilage proteoglycans and type II collagen and by stimulating the release of reactive oxygen species and prostaglandins at the sites of inflammation (1). ATP could be another key mediator, because it acts as an extracellular messenger in several systems.…”

Knee Health Promotion Option for Osteoarthritic Knee: Cartilage Regeneration is Possible

“…These proteins include glycoprotein debris and collagen fragments derived from destructed cartilaginous tissue and enzymes such as metalloproteinase, collagenase and proinflammatory cytokines (interleukin-1, interleukin-1, tumour necrosis factor , etc) (Yoshihara Y et al, 2000;Hedbom E and Hauselmann HJ, 2002;Tchetverikov I et al, 2005). All of these proteins in synovial fluid might reflect the pathological status of the knees.…”

How Important are Innate Immunity Cells in Osteoarthritis Pathology

“…Ideally, we wish to detect osteoarthritis at an early stage by following the changes in expression of particular molecular markers, assuming that these markers are sufficiently sensitive, specific, and quantitative for the disease. OA is no longer considered an exclusively degenerative joint disorder because it is related to changes in the synovial membrane as a result of more or less exerted inflammation (Hedbom & Hauselmann, 2002). Trauma or some mechanical problem might be the primary reason for OA initiation.…”