Articular Cartilage

Frank J. Frassica, MD



Important properties of articular cartilage include:

* Avascular (no blood vessels)
* Aneural (no nerve fibers)
* Alymphatic (no lymphatic vessels)
* Very low friction on cartilage on cartilage motion
* Self-renewing (maintenance and restoration of extracellular matrix)
* With aging, loss of ability to maintain the extracellular matrix

In regard to chondrocytes:

* By cartilage volume, the cells only represent about 1%.
* Chondrocytes are synthetic machines producing the extracellular matrix.
o Intracellular organelles
+ Endoplasmic reticulum
+ Golgi apparatus
* Chondrocytes do not have cell-to-cell contact in the extracellular matrix.
* With aging, chondrocytes lose their synthetic abilities.
* Chondrocytes respond to a number of stimuli:
o Increase matrix production after sensing degradation of the matrix
o Sense loads and increase matrix production
o Respond to growth factors and anabolic stimuli

Articular cartilage has three principal classes of macromolecules:

* Collagen – 60%
* Proteoglycans – 25% to 35%
* Noncollagenous proteins/glycoproteins – 15% to 20%

The three articular cartilage collagens that form cross bands are types II, IX, and XI.

Of particular note:

* Type XI binds to type II.
* Type IX binds to the cross-banded fibrils in the superficial layer.
* Type VI attaches to the matrix around the chondrocytes.
* Type X is near the calcified layer and is probably involved in mineralization of the calcified layer.

Noncollagenous proteins include:

* Decorin and fibromodulin bind to type II collagen and likely stabilize the type II collagen network.

Cartilage has a number of distinct zones.

The superficial zone has a number of important characteristics:

* Thinnest articular cartilage layer
* Two layers:
o Most superficial – fine collagen fibrils (lamina splendens)
o Deep layer – flattened fibroblast-like chondrocytes (parallel to joint surface)
* Forms a cartilage skin
* Important chemical properties:
o High collagen and low proteoglycan concentration
o Fibronectin and water concentrations are highest in this zone
* Great tensile stiffness and strength
* Seals off the cartilage from the immune system

The transitional zone lies between the superficial and middle zones of the articular cartilage.

The following important points should be remembered:

* The chondrocytes have a high concentration of synthetic organelles such as rough endoplasmic reticulum and Golgi apparatus.
* The collagen fibers are larger than in the superficial zone.
* The proteoglycan concentration is higher than the superficial zone.

The chondrocytes in the calcified cartilage zone show the least metabolic activity.

In contrast, the chondrocytes of the other areas are very active:

* Superficial zone
o Fine collagen fibrils (lamina splendens)
o High collagen and low proteoglycan concentration
o Fibronectin and water concentrations are highest in this zone
* Transitional zone
o The chondrocytes have a high concentration of synthetic organelles such as rough endoplasmic reticulum and Golgi apparatus.
o The collagen fibers are larger than in the superficial zone.
o The proteoglycan concentration is higher than the superficial zone.
* Middle (radial or deep) zone
o Largest diameter collagen fibrils
o Highest proteoglycan content

Other important points:

Interleukin I has the potential to increase expression of matrix metalloproteinases that can dissolve the extracellular matrix.

Type II collagen fibers resist tensile and shear deformation forces in the articular cartilage.

In contrast, the glycosaminoglycan aggregates resist articular cartilage compression and fluid flow.

Cyclic compressive loads have the ability to stimulate matrix synthesis – aggrecan core protein and the glycosaminoglycans.

The characteristic findings in osteoarthritis are:

* Asymmetric loss of the joint space
* Subchondral sclerosis and cysts
* Osteophyte formation

Osteoarthritis

As the cartilage degenerates, progressive bone remodeling occurs. The cause of osteoarthritis is unknown. From a chemical standpoint, one of the earliest findings is a decrease in the proteoglycan and an increase in the water content. One should remember:

* Constant type II collagen content
* Decreased proteoglycan concentration and decreased chain length
* Increased water content

The decreased proteoglycan content results in increased permeability of the cartilage. A reduction of the stiffness makes the articular cartilage less able to bear loads.

In the second stage, there is a cellular response – chondrocyte proliferation. Clusters of chondrocytes producing new matrix are visible.

In this stage, there is nitric oxide and interleukin I production. These are catabolic factors that increase matrix metalloproteinase activity. Degradative enzymes break down types IX and XI collagen, which may compromise the stability of the type II collagen framework.

In the last stage of osteoarthritis, there is reduced chondrocyte proliferation and function, which may be secondary to reduced ability to respond to anabolic factors (down regulation). There may be accumulation of molecules that bind to the anabolic factors (and keep the factors from the chondrocytes) such as decorin and insulin-dependent growth factor binding protein.

Bibliography

1. Mankin HJ, Grodzinsky AJ, Buckwalter JA. Articular cartilage and osteoarthritis. In: Einhorn TA, O’Keefe RJ, Buckwalter JA, eds. Orthopaedic Basic Science. 3rd ed. Rosemont, Ill: American Academy of Orthopaedic Surgeons; 2007:161-174.