Articular cartilage, protagonist of osteoarthritis

The process of osteoarthritis, both primary and secondary forms, occurs due to a discrepancy between the resistance of tissues and the mechanical requirements to which they are subjected. This imbalance results in the degeneration of the anatomical unit and joint physiology.

In osteoarthritis, the degenerative process starts at joint cartilage level, but during its progression it affects all the components of the joint.

The articular cartilage consists of a single cell population, the chondrocytes, which are responsible for the biosynthesis of components of the cartilage matrix, primarily collagen fibers and proteoglycans. The proteoglycans consist of a core protein linked to numerous chains of glycosaminoglycans (mucopolysaccharides).

Chondroitin Sulfate is the main glycosaminoglycan of the articular cartilage, and its main function is to maintain the elasticity and proper hydration of the cartilage.

A consequence of the osteoarthritis is the decreased concentration of Chondroitin Sulfate in the cartilage matrix, losing its ability to absorb and cushion the compressions.

The ability to regenerate cartilage is very slow. It is estimated that the rate of turnover of proteoglycans in an adult animal is more than a year.

Articular cartilage

Histology of hyaline cartilage

Hyaline cartilage plays a fundamental role in the optimal functioning of the joint, forming a smooth and sliding friction surface, which allows a correct mobility, damping and transmission of forces between the bones.

The hyaline cartilage is composed of:

- Chondrocytes or cartilage cells:
They have a limited capacity of regeneration and duplication. Their main function is to secrete the components that make up the cartilage matrix.

- Cartilage matrix or intercellular substance, composed of:

Tissue fluid: water, salts and glucose.

Proteoglycans: Responsible for maintaining a proper hydration of the cartilage. This is essential to maintain the flexibility and elasticity of the cartilage. The proteoglycans consist of a core protein bound to a number of heteropolysaccharide chains: glycosaminoglycans. The most important are Chondroitin Sulfate, Hyaluronic Acid and Sulphate Keratoses.

Collagen: Provides hardness and strength to the cartilage. In the cartilage we find mostly type II collagen, and to a much lesser extent also types IX, X and XI.

Proteoglycan structure: Protein core bound to Chondroitin sulfate and other glycosaminoglycan chains.

The molecular structure of Chondroitin Sulfate is able to retain large amounts of water molecules.

This feature allows the articular cartilage to cushion the compression forces to which it is subjected, and then recover its original shape.

Protecting the joint surface, the cartilage has four layers covering the subchondral bone:

A- Superficial or tangential layer: Responsible for sliding.
B- Intermediate or transition layer: Responsible for cushioning.
C- Radial or deep layer: Responsible for cushioning.
D- Layer of calcified cartilage: Responsible for bone anchorage.

Articular cartilage is an avascular tissue. Oxygen and nutrients are supplied by diffusion from the capillaries that surround the joint to the synovial fluid (1) from where they reach chondrocytes by circulating through the cartilage matrix fluid (2).

Osteoarthritis

It is a process of multifactorial etiology, which involves genetic, metabolic and biomechanical factors. The onset of osteoarthritis is ultimately due to the imbalance between the constant wear to which the articular cartilage is subjected, in contrast to the limited regenerative capacity of this tissue.

• Instability due to ruptured ligaments
• Overweight
• Inconsistencies: dysplasia, posttrauma,…
• Sport overuse

Structural Osteoarthritis
The joint functions normally but its structure is fragile for several reasons:

• Cartilage: chondrocalcinosis, ocronosis.
• Subchondral bone: epiphisary osteonecrosis.
• Synovial: arthritis.
• Genetics: fragile collagen, coagulopathies.
• Latrogenics: intraarticular corticosteroids, NSAIDs,…

Obese animals with neuromuscular abnormalities and hormone imbalance are prone to osteoarthritis. Rapidly growing breeds and those suffering from frequent biomechanical discrepancies, e.g. hip dysplasia, are also particularly prone.

Progression of osteoarthritis

The extent of structural defects in the OA ranges from the appearance of fissures in the surface layer to erosion into the deeper layers and formation of osteophytes. Osteoarthritis progresses through 4 stages:

• Edema cartilage: No clinical or radiological signs (detectable only by electron microscope).
• Fibrillation: Cartilage in brush, the wear affects the sliding layer.
• Fissure: Craters that affect the cushioning layer.
• Ulceration/Eburnification: The subchondral bone appears on the joint surface.

Subsequently subchondral cysts are formed due to the accumulation of detritus on the surface of bone.

In the arthritic process both the destructive agents of the joint tissue and the repair mechanisms activated by the body are involved.

Once the microstructure of the cartilage has been broken, other mechanisms, mainly proteolytic enzymes (mostly proteases and metalloproteases) from the synovial membrane, come into play and accelerate the degeneration.

These enzymes are usually balanced by the action of inhibitors, but in cases of joint damage, the balance shifts in favor of the proteases. This is probably due to an error in its regulatory mechanism, induced by the effect of inflammatory mediators. These findings have allowed proposing new mechanisms of control of osteoarthritis.