Pathophysiology Of Osteoarthritis Essay Definition

Osteoarthritis, also called osteoarthrosis or degenerative joint disease, disorder of the joints characterized by progressive deterioration of the articular cartilage or of the entire joint, including the articular cartilage, the synovium (joint lining), the ligaments, and the subchondral bone (bone beneath the cartilage). Osteoarthritis is the most common joint disease, although estimates of incidence and prevalence vary across different regions of the world and among different populations. By some estimates nearly 10 percent of men and about 18 percent of women over age 60 are affected by the condition. Although its suffix indicates otherwise, osteoarthritis is not characterized by excessive joint inflammation as is the case with rheumatoid arthritis. The disease may be asymptomatic, especially in the early years of its onset. As it progresses, however, pain, stiffness, and a limitation in movement may develop. Common sites of discomfort are the vertebrae, knees, and hips—joints that bear much of the weight of the body.

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arthritis: Osteoarthritis

Osteoarthritis, also known as degenerative joint disease, is the most common form of arthritis, affecting nearly one-third of people over age 65. It is characterized by joint pain and mild inflammation due to deterioration of the articular cartilage that normally cushions joints. Joint pain…


The cause of osteoarthritis is not completely understood, but biomechanical forces that place stress on the joints (e.g., bearing weight, postural or orthopedic abnormalities, or injuries that cause chronic irritation of the bone) are thought to interact with biochemical and genetic factors to contribute to osteoarthritis. Early stages of the condition are characterized by changes in cartilage thickness, which in turn are associated with an imbalance between cartilage breakdown and repair. The cartilage eventually becomes softened and roughened. Over time the cartilage wears away, and the subchondral bone, deprived of its protective cover, attempts to regenerate the destroyed tissue, resulting in increased bone density at the site of damage and an uneven remodeling of the surface of the joint. Thick bony outgrowths called spurs sometimes develop. Articulation of the joint becomes difficult.

Depending on the site and severity of the disease, various treatments are employed. Individuals who experience moderate symptoms can be treated by a combination of the following: analgesic (pain-relieving) medications, periodic rest, weight reduction, corticosteroid injections, and physical therapy or exercise. Surgical procedures such as hip or knee replacement or joint debridement (the removal of unhealthy tissue) may be necessary to relieve more severe pain and improve joint function.

By Shari M. Ling, M.D. and Joan M. Bathon, M.D.

Although epidemiological studies have promoted our understanding of the risk factors that predispose to OA, we do not yet understand the initiating events that trigger the disease.

OA is primarily a disease of cartilage

Cartilage is a unique tissue with viscoelastic and compressive properties which are imparted by its extracellular matrix, composed predominantly of type II collagen and proteoglycans.

Under normal conditions, this matrix is subjected to a dynamic remodeling process in which low levels of degradative and synthetic enzyme activities are balanced, such that the volume of cartilage is maintained. In OA cartilage, however, matrix degrading enzymes are overexpressed, shifting this balance in favor of net degradation, with resultant loss of collagen and proteoglycans from the matrix.

Presumably in response to this loss, chondrocytes initially proliferate and synthesize enhanced amounts of proteoglycan and collagen molecules. As the disease progresses, however, reparative attempts are outmatched by progressive cartilage degradation. Fibrillation, erosion and cracking initially appear in the superficial layer of cartilage and progress over time to deeper layers, resulting eventually in large clinically observable erosions. OA, in simplistic terms, therefore, can be thought of as a process of progressive cartilage matrix degradation to which an ineffectual attempt at repair is made.

Is OA simply a process of aging of cartilage?

A critical question is whether OA is truly a disease or a natural consequence of aging. Several differences between aging cartilage and OA cartilage have been described, suggesting the former. For example, although denatured type II collagen is found in both normal aging and OA cartilage, it is more predominant in OA. In addition, OA and normal aging cartilage differ in the amount of water content and the in ratio of chondroitin-sulfate to keratin sulfate constituents. The expression of a chondroitin-sulfate epitope (epitope 846) in OA cartilage, that is otherwise only present in fetal and neonatal cartilage, provides further evidence that OA is a distinct pathologic process. A final but important distinction is that degradative enzyme activity is increased in OA, but not in normal aging cartilage.

What molecules are responsible for degrading cartilage matrix?

The primary enzymes responsible for the degradation of cartilage are the matrix metalloproteinases (MMPs).

These enzymes are secreted by both synovial cells and chondrocytes and are categorized into three general categories: a) collagenases; b) stromelysins; and, c) gelatinases. Under normal conditions, MMP synthesis and activation are tightly regulated at several levels. They are secreted as inactive proenzymes that require enzymatic cleavage in order to become activated. Once activated, MMPs become susceptible to the plasma-derived MMP inhibitor, alpha-2-macroglobulin, and to tissue inhibitors of MMPs (TIMPs) that are also secreted by synovial cells and chondrocytes. In OA, synthesis of MMPs is greatly enhanced and the available inhibitors are overwhelmed, resulting in net degradation. Interestingly, stromelysin can serve as an activator for its own proenzyme, as well as for procollagenase and prostromelysin, thus creating a positive feedback loop of proMMP activation in cartilage.

What factor(s) is responsible for inducing metalloprotease synthesis?

One candidate is interleukin-1 (IL-1). IL-1 is a potent pro-inflammatory cytokine that, in vitro, is capable of inducing chondrocytes and synovial cells to synthesize MMPs.

Furthermore, IL-1 suppresses the synthesis of type II collagen and proteoglycans, and inhibits transforming growth factor-ß stimulated chondrocyte proliferation. The presence of IL-1 RNA and protein have been confirmed in OA joints. Thus, IL-1 may not only actively promote cartilage degradation, but may also suppress attempts at repair, in OA. In addition to these effects, IL-1 induces nitric oxide production, chondrocyte apoptosis, and prostaglandin synthesis, which further contribute to cartilage deterioration. Under normal conditions, an endogenous IL-1 receptor antagonist regulates IL-1 activity. A relative excess of IL-1 and/or deficiency of the IL-1 receptor antagonist could conceivably result in the cartilage destruction that is characteristic of OA. It is likely that other cytokines or particulate material from damaged cartilage may also contribute to this inflammatory, degradative process.

Can cartilage repair itself?

Growth factors are produced locally in cartilage and synovium and are likely to contribute to local cartilage remodeling by stimulating the de novo synthesis of collagen and proteoglycans. Transforming growth factor ß (TGFß) is the best characterized and most potent of the chondrocyte growth factors. Not only does TGFß stimulate de novo matrix synthesis, but it also counteracts cartilage degradation by down regulating IL-1 receptor expression and by increasing IL-1 receptor antagonist release and TIMP expression. Insulin-like growth factor (IGF-1) and basic fibroblast growth factor (b-FGF) are also present in OA cartilage and likely to contribute to reparative attempts, although, as noted, degradation ultimately outstrips repair in OA cartilage.


In summary, MMPs and pro-inflammatory cytokines (e.g., IL-1) appear to be important mediators of cartilage destruction in OA. Synthesis and secretion of growth factors and of inhibitors of MMPs and cytokines are apparently inadequate to counteract these degradative forces. Progressive cartilage degradation and OA result. New therapies (see Treatment), focused on reducing MMP activity and on stimulating matrix synthesis, are in development.


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Updated: March 27, 2012

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