The Role of Cytokines in Osteoarthritis

Mechanical Osteoarthritis

Inflammation and accompanying dysregulated cytokine catabolic activities play key roles in OA pathogenesis in addition to the effects of age and excessive mechanical loading (for review, see 70,74,121 (Fig. 3.2). Osteoarthritis is not considered a classical inflammatory arthropathy, because of the absence of neutrophils in the synovial fluid and the lack of systemic manifestations of inflammation. Nevertheless, synovial inflammation is common in both early and late stages of OA 19 . The...

Osteoarthritis Prevalence and Risk Factors

It is well known that OA differs in men and women. Men younger than 50 tend to be most affected by OA, whereas, in people over 50, two thirds of the OA patients tend to be women 69 . The reason for this is unclear. Osteoarthritis in younger men is considered to be an occupational disease. In contrast, the high incidence in postmenopausal women suggests that the change in hormonal status may play a role in the OA process. However studies dealing with the protective effect of estrogens show...

Cartilage Matrix Synthesis in Osteoarthritis

In early stages of OA, the synthesis of matrix proteins is altered. Genomic and proteomic analyses of global gene expression have detected an increase in type II collagen gene (COL2A1) expression in early OA cartilage 3,16,87 , possibly associated with the increased levels of anabolic factors such as bone morphogenetic protein-2 (BMP-2) and inhibin A activin 63,87,158 . These and other TGF-P family members may stimulate aggrecan synthesis at the same time as promoting the formation of...

The Chondrocyte in Osteoarthritis

Osteoarthritis is defined largely as a disease of cartilage, since the chondrocytes, which constitute the unique cellular component of adult articular cartilage, are able to respond to mechanical injury, joint instability due to genetic factors, and biologic stimuli such as cytokines and growth and differentiation factors (Fig. 3.1). In young individuals without genetic abnormalities, biomechanical factors due to trauma are strongly implicated in initiating the OA lesion 95,114 , and mechanical...

Possible Interaction of Bone and Cartilage in Osteoarthritis

An earlier concept that targeted repair of the subchondral bone is initiated in response to the formation of microfractures was revived when it was observed that the elastic modulus (stiffness) of the tissue was reduced locally due to an increase in vascularization and in the remodeling rate 40 . These changes would lead to reactivation of the secondary ossification center and a decrease in cartilage thickness 30 . The concept that modified remodeling or bone turnover causes cartilage...

Info

Synovial membrane (subchondral) bone joint deformation cartilage destruction capsular fibrosis synovial hyperplasia (subchondral) bone remodeling and sclerosis osteophyte formation Figure 1.3. Overview of the pathologic changes associated with OA. Apart from cartilage destruction, fibrosis of the synovial capsule, hyperplasia of the synovial membrane, subchondral bone remodeling, and osteophyte formation contribute to the disease. (Adapted from Aigner and Stove 4 .) joint deformation cartilage...

Signaling Pathways Regulated by Cytokines

Interleukin-1 and TNF-a share common signal transduction pathways, and the key signaling molecules involved are targets for therapy 21,132 . The major pathways induced by catabolic cytokines involve signal transduction by the stress-activated protein kinases c-Jun N-terminal kinases (JNKs) and p38 kinases and the nuclear factor (NF)-kB IkB pathway. In vitro studies in chondrocytes have shown that the p38 and JNK cascades mediate the induction of proteinases and proinflammatory genes by IL-1 and...