DEFINING OSTEOARTHRITIS

Ostcoarthritis is no a single disease, but an extremely common group of disorders that affect synovial joints and are linked to advancing age. A satisfactory clinical definition of osteorathritis has not been determined due to the heterogeneity of the condition and the fact that it can result from a number of different joint insults. Although definitions of osteorthritis vary, most acknoledge that osteoarthritis is characterized by degenerative changes in articular cartilage. Thus, osteoarthritis has been difined as an inherently noninflammatory disorder of movable joints characterized by deterioration of articular cartilage and by the formation of new bone at the joint surfaces and margins.

Osteoarthritis has also been defined as a combination of interactive degradative and repair process in cartilage, bone, and synovium with secondary components of inflammation. Although originally thought of as a noninflammatory, hypertrophic form of arthritis, osteoarthritis is now known to involve a disruption in the normal balance between cartilage synthesis and degradation, often involving some degree of inflammation.

A third definition, offered by the American College of Rheumatology (ACR), defines osteoarthritis as a heterogeneous group of conditions that lead to joint symptoms and signs which are associated with defective integrity of articular cartilage, in addition to related changes in the underlying bone at the joint margin.

Joint Physiology

Osteoarthritis is primarily a disorder of articular cartilage and subchondral bone, However, all tissues of the synovial joint are involved in the disease process.

Articular Cartilage

Articular  cartilage distributes loads over bone surfaces and provides a low friction surface over which bones can move. The articular cartilage contains no blood vessels, nerves, or lymphatic vessels, and is largely composed of extracellular matrix tissue. Only 1% to 2% of the cartilage volume is occupied by cells, while 98% to 99% of the tissue volume is composed of matrix tissue.

Chondrocytes

 The cells of articular cartilage are called chondrocytes. Although these cells are metabolically very active, they normally do not divide after adolescence. Since articular cartilage contains no blood vessels, chondrocytes must receive their nutricnts by diffusion from the underlying subchondral bone, or from the synovial fluid that bathes the cartilage surface. These cells are responsible for the production and maintenance of the extracellular matrix.

Extracellular Matrix

The critical biomechanical properties of articular cartilage depend on the integrity of its extracellular matrix. The three primary constituents of the extracellular matrix are proteoglycans, type II collagen and water.

Proteoglycans

Proteoglycans make up most of the volume of the extracellular matrix and are responsible for the stiffness of the tissue. As many as 200 large proteoglycan molecules (called aggrecan) assemble around a hyaluronic acid chain to form conglomerates, or aggregates. The molecular structure of these aggregates creates an overall negative charge, which attracts molecules of water. Together, the water and proteoglycan aggregates are restrained by a network of crosslinked collagen fibers.

Aggrecan consists of a protein core in which proteoglyean molecules, such as chondroitin sulfate, are attached. About 100 chondrohin sulfate chains and about 30 keratan sulfate chains are attached to a single core protein. The protein and its attached chains are referred to as an aggreean monomer. About 100 agrecan monomers are linked to a string of byaluronic acid to form a proteoglycan aggregate. Other proteoglycans and proteins have been identified in articular cartilage. Compounds such as fibromodulin, fibronectin, and anchorin II may play important roles in maintaining the integrity and function of the extracellular matrix tissue.

Collagen

 This type of collagen is found in only a few other body tissues. Smaller quantities of types IX, X, XI and VI collagen may also be found. In the extracellular matrix, type II collagen, forms a tight network that restricts the hydration and expansion of the proteoglycan aggrecans. This collagen network provides articular cartilage with tensile strength between and resistance to shearing forces, Type IX collagen forms cross links between the collagen fibers, increasing the strength of the collagen "net". It also forms links between the collagen fibers and aggrecan molecules. Type X and type VI collagen are associated with metabolically active chondrocytes. Their levels may be increased in patients with osteoarthritis.

Water

When weight is applied to a joint and the cartilage is compressed, water molecules are forced out of the extracellular matrix. When the pressure is removed, water moves back into the matrix until the swelling pressure of the proteoglycans is balanced by the resistance of the collagen network. This gives articular cartilage the property of reversible deformation.