36.1 Articular Cartilage: Composition

It is considered by many that the most important structure within a synovial joint is articular cartilage, otherwise known as hyaline cartilage. This tissue is the smooth, glistening white material covering the articulating bone ends and serves to provide frictionless joint movement. For the vast majority of individuals, it will act in a trouble-free manner over their lifetime. Cartilage is remarkably resilient to compressive forces, which can exceed 100 atmospheres during standing,1 yet allows controlled deformation in order to distribute loads. It is all the more remarkable, therefore, that articular cartilage is alymphatic, aneural, and avascular. Furthermore, it is 65 to 80% water by wet weight.2 Given the avascular nature of cartilage, its nutrition is entirely reliant on the diffusion of metabolites from the synovial fluid.

The chondrocyte is the only cellular component of articular cartilage. Chondrocytes comprise less than 10% of the structure of cartilage and contribute approximately 1% of its volume. 3 They exhibit a very simple rounded shape when viewed under a microscope (Fig. 36.1). Despite their simplistic appearance, however, chondrocytes are actually highly differentiated and specialized mesenchymal cells that are central to the survival of cartilage.1

The primary role of the chondrocyte is to synthesize the macromolecular components that constitute the extracellular matrix. These components include collagen, proteoglycans, and noncollagenous proteins.3 The final addition to these macromolecular components, in the extracellular matrix, is tissue fluid, which is predominantly water. The extracellular matrix is thereby essentially a fiber-reinforced gel. It is the interaction between the macromolecular framework and tissue fluid that provides cartilage with its unique mechanical properties of “stiffness” and “resilience.”

Throughout their lifespan, chondrocytes have an intimate relationship with the extracellular matrix. Alterations in the macromolecular composition of the matrix are closely monitored by the chondrocytes and, when necessary, controlled matrix synthesis or breakdown is initiated. Chondrocytes are therefore both the architects and cellular building blocks of articular cartilage.

Chondrocytes are regarded as postmitotic cells, insomuch that once skeletal maturity is reached there is no further cell division detectable in healthy adult articular cartilage.1 Mature chondrocytes therefore have a long lifespan and are generally expected to remain viable as long as their host.

Once chondrocytes are lost they are not replaced, and when they are lost in large numbers their importance in the maintenance of cartilage integrity is truly illustrated. Simon et al, 4 investigating the long-term effect of chondrocyte death induced by localized cryotherapy on rabbit articular cartilage in vivo, demonstrated, through histological staining coupled with both normal and polarized light microscopy, that the cartilage was structurally intact at 6 months despite the absence of living chondrocytes. However, by 12 months extensive cartilage fibrillation and softening was evident, changes which are considered to be among the first macroscopic appearances associated with degenerative joint disease.

There is currently no accurate information as to the length of time taken for human cartilage devoid of chondrocytes to degrade. Nevertheless, the progressive degeneration and loss of cartilage will be inevitable. It is therefore extremely important to preserve chondrocyte viability during both acute and chronic pathology, and also during surgical instrumentation.

36.2 Articular Cartilage: Structure

Despite the apparently simplistic composition of articular cartilage, its structure is both complex and heterogeneous. The thickness, cell density, matrix composition, and mechanical properties of articular cartilage vary within the same joint, between joints in the same individual, and between species. 5 Nevertheless, a consistent feature of articular cartilage within synovial joints, regardless of species, is that it has the same overall structure and serves the same function.

The full thickness of cartilage extends from the articular surface to the osteochondral junction (bone-cartilage interface) (Fig. 36.1). Between these two points, articular cartilage is loosely divided into four distinct zones on the basis of depth-associated variation in cell morphology and extracellular matrix properties1: the superficial zone,2 the middle zone,3 the deep zone,4 and the zone of calcification (Fig. 36.1).3 The demarcation between each zone, however, can often be difficult to define.

The superficial (tangential) zone is the smallest zone, accounting for approximately 0 to 10% depth from the articular surface and typically consists of two layers (Fig. 36.1).5 The first of these layers is an acellular sheet of fine fibrils that is known as the lamina splendens.3 Deep to this layer, flattened ellipsoid-shaped chondrocytes lie within a matrix that has a low proteoglycan and high collagen content. 6 The dense network of collagen fibers, which, along with the chondrocytes, are orientated parallel to the articular surface, provide the tissue with tensile strength and stiffness. This arrangement is also considered to act as a sieve by allowing the passage of nutrients from the synovial fluid into the cartilage while, at the same time, preventing the ingress of potentially damaging larger molecules of the immune system.3

The middle zone provides a functional and anatomical bridge between the superficial and deep zones. It accounts for approximately 10 to 40% depth from the articular surface (Fig. 36.1). The chondrocytes within this zone are at lower density and are more spherical in shape in comparison to the superficial zone. The collagen fibers have a greater diameter and, in contrast to the superficial zone, arch obliquely in relation to the articular surface. Furthermore, there is a greater concentration of proteoglycans within the matrix of this zone but, conversely, there is a lower water and collagen content.5 Functionally, the middle zone offers the first line of resistance to compressive forces and thereby acts as a “shock absorber.”

Immediately below the middle zone lies the deep zone, which accounts for approximately 40 to 100% depth from the articular surface (Fig. 36.1). It is characterized by spherical chondrocytes that organize themselves into columns, sometimes referred to as “Benninghoff′s arcades,” that are perpendicular to the articular surface. The adjacent collagen fibers, which have the widest diameter of all collagen fibers embedded within articular cartilage, extend into the tidemark, the boundary between uncalcified and calcified cartilage.3 The main function of this zone, which contains the highest concentration of proteoglycans and the lowest water content, is to provide the maximum resistance to compressive forces.2

The deepest layer of cartilage is the zone of calcification, otherwise known as the zone of calcified cartilage, and this layer separates articular cartilage from subchondral bone (Fig. 36.1). This zone is characterized by a sparse population of spherical chondrocytes that are of a lower volume than those from the deep zone. The chondrocytes are surrounded by uncalcified lacunae and radial collagen fibers that are anchored within a calcified matrix in which there is an absence of proteoglycans.6 The zone of calcification plays a crucial role in tethering cartilage to bone.

36.3 Cartilage Repair

It is well recognized that articular cartilage has a very poor regenerative capacity following injury. There are two likely explanations for this phenomenon. Firstly, as mentioned previously, the literature to date suggests that cellular division does not take place in healthy articular cartilage chondrocytes once skeletal maturity has been reached. Chondrocyte loss, as a consequence of injury or disease, in adulthood is therefore not replaced. Secondly, cartilage is an avascular tissue. In well-vascularized tissues such as skin and liver, the healing process follows an established pattern of necrosis, inflammation, and repair. An adequate blood supply is essential for the inflammation and repair phases of the response. Necrosis has been shown to be present in partial thickness articular cartilage injuries but no healing process has subsequently been identified. 7 However, if the injury extends beyond the zone of calcification (see the previous discussion), blood seeps into the wound from the vascularized subchondral bone, thereby delivering the necessary inflammatory mediators, growth factors, and reparative cells, such as fibroblasts and mesenchymal stem cells, for healing to occur. Nevertheless, the healing process that ensues is rudimentary and the defect is filled with mechanically inferior fibrocartilage. This suboptimal tissue has been shown to degenerate quickly once mechanical load is applied with the eventual formation of an isolated osteoarthritic lesion that may subsequently result in pain and disability.7