Biomedical Engineering Reference
In-Depth Information
261
]. The subchondral bone remodels with thickening as it is now unprotected from the load
borne by cartilage [
262
,
263
]. The bone may be entirely exposed as cartilage is denuded during the
disease's progression. Along with the thickening, new bone formation is observed. The remodeling
and formation of osteophytes, which arise from the bony margins of the joint, alter the contours of
the joint. Osteophytes are strongly associated with malalignment [
264
-
266
], an identified cause for
cartilage lesions that can lead to further degeneration. Depending on the joint location, the cartilage
can be white to yellow or brownish, with generally decreased mechanical properties, though there
can be regions where the new, healthy-looking cartilage has formed in small, pebbled patterns.
Destruction of the cartilage surface in OA occurs in phases. During the development of
the disease, no visual, functional, or mechanical alterations appear detectable. Fibrillation, surface
erosion, and fissures are the first noticeable signs of the disease. From this point on, altered histological
staining will show continued decreases in proteoglycan content. The tidemark begins to appear
irregular, punctuated with blood vessels. A second stage of the disease shows greater surface wear
and irregularity. Vertical and sometimes horizontal fissures can be seen in the cartilage. Proteoglycans
start to leave from the fissures and an absence of staining will spread from these areas to the rest of the
tissue. These patterns of increased tissue fragmentation and decreased staining continues until the
cartilage, completely robbed of its abilities to withstand load, is worn away to expose the subchondral
bone. During these cartilage changes, bone and synovium remodeling occurs as described previously.
When considering this cascade of events, it is not surprising to note that OA cartilage possesses
inferior mechanical properties. The gradual proteoglycan loss is a first hint. However, OA cartilage
also increases in water content, an observation that appears counter-intuitive, as it is the negative
charges on the proteoglycans that attract ions to increase the osmotic pressure that drives hydration
in this tissue. Lowered proteoglycans are thus expected to lower the Donnan osmotic pressure and
result in water loss. It is postulated that the observed increase in hydration is due to the loosening of
the proteoglycan network to allow for macromolecular un-curling, thus allowing for more interstitial
space for water to occupy.This theory is supported by the observations that the fraction of aggregating
proteoglycans decrease with OA and that the proteoglycans are increasingly more extractable with
disease progression. Being unable to aggregate, the proteoglycans are thus unable to pack as densely,
supporting the uncurling hypothesis. Greater extractability is likely a result of decreased molecular
weight or, as has been shown, the result of damaged link proteins that no longer facilitate the
formation of aggrecan. In addition, the catabolic agents released during OA can loosen the collagen
network, too, to result in more space for water to occupy. Tensile strength, attributed to the collagen
in cartilage, has been shown to decrease with OA.
2.4.2 PROLIFERATION, CATABOLISM, ANDCELLDEATH
The cellular behavior in OA can be classified into three stages. With changes occurring in the intert-
erritorial and territorial matrices, the chondrons, where the chondrocytes reside, may become swollen
and distended, signaling the cells to proliferate to fill up the additional space. IL-1 upregulation then
initiates the destruction of the fibrillar collagen environment, which results in additional chondron
