It is believed that feel that the primary changes in OA begin in the cartilage. A change in the arrangement and size of the collagen fibers is apparent.
The biochemical data are consistent with the presence of a defect in the collagen network of the cartilage, perhaps due to disrupation of the glue that binds adjacent fibers together in the matrix.
This is among the earliest matrix changes observed and appears to be irreversible.
Wear may be a factor in the loss of cartilage but there is a strong eveidence that lysosomal enzymes and matrix metalloproteinases account for much of the loss of cartilage matrix in osteoarthritis. Whether their synthesis and secretion are stimulated by Interleukin-1 or by other factors (e.g., mechanical stimuli), matrix metalloproteinases, plasmin, and cathepsins all appear to be involved in the breakdown of articular cartilage on OA.
Tissue inhibitor of metalloprteinases may work to stabilize the system, at least temporarily, while growth factors, such as Insulin growth factor, and basic fibroblast growth factor are involved in repair processes that may heal the lesion or, at least, stabilize the process.
A stoichiometric imbalance exists between the levels of active enzyme and the level of tissue inhibitor of matrix metalloproteinases, which may be only modestly increased.
The chondrocytes in OA cartilage undergo active cell division and are very active metabolically, producing increased quantities of DNA, RNA, collagen, PG, and noncollagenous proteins. Prior to cartilage loss and PG depletion, this marked biosynthetic activity may lead to an increase in prostaglandin concentration, which may be associated with thickening of the cartilage and a stage of homeostasis referred to as “compensated” OA.
These mechanisms may maintain the joint in a reasonably functional state for years. The repair tissue, however, often does not hold up as well under mechanical stresses as normal hyaline cartilage, and eventually, at least in some cases, the rate of PG synthesis falls off and “end-stage” OA develops, with full-thickness loss of cartilage.
Popularity: 1% [?]
Join Discussions