Review Question - QID 219378

The quantity of the glycosaminoglycan, aggrecan, increases in the early stages of osteoarthritis, but decreases in the later stages.

Articular cartilage breakdown occurs in the setting of osteoarthritis. As injury to the cartilage occurs, biologic changes take place at a microscopic level that lead to alterations in this environment. Matrix metalloproteases and aggrecanases tend to increase in quantity, causing breakdown of the primary components of cartilage. Studies have demonstrated that an initial increase in aggrecan occurs as a protective effect, followed by a steady decline in aggrecan content long term which leads to decreased glycosaminoglycan content. As the cartilage surface breaks down, water tends to flow in causing swelling and leading to increased elasticity and decreased strength. All of these factors contribute to the overall development of osteoarthritis which is significant for loss of articular cartilage.

Mort and Billington published a review article detailing the changes in articular cartilage with matrix degradation in arthritis. They note that enzymatic changes due to an increase in matrix metalloproteases and aggrecanases (ADAMTSs) are primarily responsible for this degradation. The metalloproteases are typically responsible for breaking down the triple helix of collagen, while the ADAMTSs degrade aggrecan, leading to the long term decrease in it's quantity.

Martin and Buckwalter evaluated the effects of articular cartilage with aging and osteoarthritis, noting that aging does not necessarily guarantee the development of arthritis, despite their association. They note that changes in articular cartilage relate to a long term decrease in aggrecan and a loss of tensile strength and stiffness. They also mention a theory that suggests progressive chondrocyte senescence in this population with erosion of chondrocyte telomere length due to oxidative damages.

Roughley and Mort looked at the role of aggrecan in normal and osteoarthritic cartilage. They note during the early stages of osteoarthritis, the production of aggrecan may increase in order to prevent further overall degradation. However, during the later stages, as aggrecanases increase in activity, the quantity sharply decreases and affects the quality of the cartilage negatively.

Incorrect Answers:
Answer 1: Water content uniformly increases in osteoarthritis due to structural changes that lead to increased tissue permeability and cartilage swelling.
Answer 2: Matrix metalloprotease quantity uniformly increases during the arthritis process as these enzymes are thought to be a key contributor to cartilage breakdown.
Answer 3: The ratio of chondroitin sulfate:keratan sulfate uniformly increases in the setting of osteoarthritis.
Answer 4: The Young's modulus of elasticity tends to follow a linear decrease in the setting of osteoarthritis, as cartilage looses its stiffness throughout the process without any period of initial increase.