Articular Cartilage And Osteoarthrosis

ARTIGO DE REVISÃO

Articular cartilage and osteoarthrosis

Márcia Uchôa of Rezende; Arnaldo José Hernandez; Gilberto Luís Camanho; Marco Martins Amatuzzi

INTRODUCTION

Currently, the mechanical degenerative changes of the articular cartilage are one of the primary concerns among orthopedic experts.

Both the difficulty in establishing experimental models of arthrosis and the regular observation of secondary arthritic phenomena in typically orthopedic diseases - like sequelae from fractures and articular instability - are aspects which close the orthopedist to the study of the cartilage and its physiology.

The objectivity of orthopedics becomes this interest and proximity hard. The study of either the cartilage biology or its structure and degeneration is based on concepts few common to our literature. However, the knowledge of the pathophysiology of the osteoarthrosis has demonstrated that a biological solution is very close, especially in the initial cases. The use of either therapeutically or preventively systemic or intra-articular drugs is already incorporated in our arsenal.

The aim of this review article is to offer briefly to the orthopedist the study of the cartilage physiology and the osteoarthrosis pathophysiology.

THE NORMAL ARTICULAR CARTILAGE

It is known that the articular cartilage is an avascular and poorly cellular tissue, whose biochemical characteristics reflect mainly the composition of the extracellular matrix (Lanzer & Komenda, 1990). The extracellular matrix is hyperhydrated (the water content ranges from 66% to 80%), with 20%-34% of solid components, 5%-6% of which is inorganic components (hydroxyapatite). Among the remaining organic content, 48%-62% is formed by type-II collagen and 22%-38% is formed by proteoglycan. The rigidity and elasticity of the tissue are consequence of the relative decompressibility of the proteoglycan molecules. The thick bundle of collagen fibers underlying and paralleled to the articular surface form a "skin" and probably serve not only as a restrictive layer but also as a distributor of compression strengths. The fibers of the cartilage basal layer are perpendicular to the surface and they serve as an anchor, which fasten the decalcificated cartilage to the calcified zone and perhaps to the subchondral bone. In the intermediate zones, the fibers are randomly disposed. The oblique fibers probably aid in the resistance to tensions. (Brandt and Mankin, 1993)

In the normal metabolism of the cartilage, the chondrocyte guides the matrix components recycling (probably enzyme-mediated) to satisfy the internal needs of remodeling. In the normal adult tissue the homeostasis of the matrix is balanced to avoid either losses or gains of tissue. These processes are controlled by a variety of proteins named growth factors and cytokines. (Pelletier and cols., 1993)

Growth factors [Insulin-like growth factor-1 (IGF-1) and Transforming growth factor-beta (TGF-b)] stimulate the agrecan (a predominant type of proteoglycan) and collagen synthesis. They can modulate the anabolic and catabolic pathways of the chondrocyte metabolism (e.g., they can increase the proteoglycan synthesis) (Morales, 1990).

Acid proteases, glycosidases and sulphatases (autolytic cellular enzymes, mainly the lysosomal enzymes) mediate the proteoglycan degradation (Ehrlich, 1985).

Cytokines, such as interleukin-1 (IL-1), interleukin -6 (IL-6) and the alpha tumor necrosis factor (FNT-a) stimulate the matrix degradation. The IL-1 is a protein of low molecular weight produced by synovial mononuclear and chondrocyte cells. The IL-1 mediates the collagenase and proteases release, which degrade proteoglycan by the chondrocyte. The IL-1 stimulates the synthesis and the release of stromelysine, which is capable to activate the pro collagenase inside the cartilage. The tumor necrosis factor (FNT) has similar activity but its effect on chondrocytes is less potent than the effect of the IL-1. The role of the IL-6 in the osteoarthrosis is not well defined. It is known that in vivo they activate B and T lymphocytes, which can contribute to the synovial changes found in the osteoarthrosis (Pelletier and cols., 1993).

The cartilage has tecidual inhibitors of metalloproteinases that inhibit the activities of the collagenase and stromelysine. (Dean and Woessner, 1985)

THE PATHOLOGICAL ARTICULAR CARTILAGE - OSTEOARTHROSIS

In either primary or secondary osteoarthrosis, the cartilage is the tissue with the largest deviations from the usual. Among morphologic changes, the articular cartilage loses its homogeneous nature and it is broken and fragmented, with fibrillation, fissures and ulcerations. Sometimes, according to the evolutive course of the disease, no cartilage remains and areas of subchondral bone are exposed. The staining histochemistry techniques of the matrix for proteoglycan are unequal and the separation line between the calcified cartilage and the radial zone is invaded for capillaries. A cluster of cells is formed (Moskowitz, 1973 and Muir, 1977). Osteophytes are covered by hyaline cartilage and fibrocartilage newly formed showing great irregularity in its structure (Marshall, 1969).

It is known that, among the metabolic changes, the synthesis and secretion rates of enzymes that degrade the matrix by chondrocytes are increased. Either the lysosomal or extralysosomal enzymatic activity is increased in several times. These enzymes are metalloproteinases (collagenase, stromelysine and gelatinase) and the hyaluronidase, which led to degradation of the cellular cluster and loss of proteoglycans of the matrix. They also lead to the cleavage of the hyaluronic acid and the 6-sulphate chondroitin. They produce proteoglycans unable to cluster and they degrade the type-II collagen; Also, they promote the degradation of the proteoglycan carcass, the activation of other enzymes, such as pro-stromelysine (which degrades the matrix) and stromelysine. Stromelysine activates the collagenase to destroy the collagen, which is the main factor in the progression of the disorder and the primary aspect in the final destruction of the surface (Ryu and cols., 1984 and Pelletier and cols., 1993).

The IL-1 is considered the first agent for the degradation of the cartilaginous matrix once it stimulates the synthesis and the secretion of several enzymes of degradation, including the latent collagenase, stromelysine, gelatinase and the tecidual plasminogen activator. (Pelletier and cols., 1993)

In the initial phase of osteoarthrosis there is an increased synthesis of proteoglycans, collagen, non-collagen proteins, hyaluronate, and desoxyribonucleic acid (DNA) (Ryu and cols, 1984), indicating cellular replication and justifying the chondrocyte cluster which are histologically observed (Marshall, 1969; Moskowitz, 1973; Muir, 1977). Later, the collagen and proteoglycan synthesis increases according to the severity of the damage. With the severity of the disease, the proteoglycan synthesis declines significantly, i.e., the chondrocyte "fails" (Mankin, 1971).

PATHOPHYSIOLOGY OF THE SECONDARY OSTEOARTHROSIS

The orthopedist often deals with the secondary osteoarthrosis, which is nearly always due to axis deviations or post traumatic.

The experimental model of partial meniscectomy in rabbits (Moskowitz, 1973) and the canine model of anterior ligament injury (Marshall, 1969; Pond-Nuki, 1973; Muir, 1977) allowed the study of the early changes of the secondary arthrosis and the knowledge that its first change is the increase of the cartilage water content. The cause of this hyperhydration is unknown. Perhaps it occurs due to a failure in the elastic restrictive action of the collagen net, which allows the proteoglycan (hydrophilic) to swallow abnormally. Due to the cartilage hyperhydration, proteoglycans are more easily extracted from the matrix. There is loss of the orientation of the collagen close to the surface and also an abnormal separation between the fibers. Thus, there is loss of the rigidity and elasticity to compression. The composition of newly synthesized proteoglycans has larger proportion of chondroitin sulphate and smaller proportion of keratosulphate (McDevitt and cols., 1974). The proteoglycan aggregation is harmed (McDevitt and Muir, 1976). All these changes occur before the fibrillation or prior to any other morphologic change is evident and when the proteoglycan concentration is normal or increased (this explains the general decrease of rigidity that occurs in the underlying fibrillation areas) (Kempson and cols., 1971). In the natural course of the disease, there is growth of cartilage focal ulcerations. It may be found proteoglycans loss and worsening in their aggregation, persistence of abnormalities in the composition of the glycosaminoglycans and decrease of chondroitin sulphate long chains. As the proteoglycan loss increases, the initial water content falls below the normal.

The destruction of the cartilaginous structure and subsequent exhibition of the subchondral bone sustain a cycle in those patients with osteoarthrosis.

THE FUNCTION OF HYALURONAN IN THE ARTICULATIONS

structural and lubricant function

Hyaluronan (AH) is an alternative name for the hyaluronic acid, which describes the molecule of the acid apart from its dissociation state from carboxyl radical. In the cartilage either cartilage chondrocytes or fibroblasts of the synovial layer (also named B cells) synthesize hyaluronan. The AH synthesized by cartilage chondrocytes is integrated into the cartilaginous matrix while the AH of the synovial cell is released in the articular cavity (Abatangelo and Reagan, 1995).

The importance of the AH in the articular cartilage is related to the maintenance of the agrecan structure. The proteoglycan molecules (agrecan) join to the chains of AH to form large clusters whose molecular weight is up to 10⁸ Da. These macromolecules are deposited in the collagen net. The integrity of the proteoglycan cluster is directly related to the integrity of the AH. Although the concentration of AH in the cartilage increases with aging, its molecular weight is reduced which lead to smallest proteoglycan attachés. As the newly synthesized molecules of AH show few changes with the aging it is supposed that there is an extracelular breakdown of the molecule with aging. Similarly, in the osteoarthrosis (OA), the AH is depolymerized with consequent rupture of proteoglycan attachés and subsequent deterioration of the mechanical properties of the tissue (Abatangelo and Reagan, 1995).

AH with a molecular weight of thousands of Daltons are present in the normal synovial fluid in concentrations ranging from 2-4 mg/ml (Balazs and Denlinger, 1993). The combination between high molecular weight and concentration results in a solution highly viscous and elastic with either lubrication or shock absorption function under high strengths (Bothner and Wik, 1987). An important element in the pathophysiology of OA is the loss of viscous and elastic properties of the synovial fluid due to the decrease of concentration and molecular weight of the AH (Balazs, 1974). The reduced viscosity and elasticity of the synovial fluid increases the cartilage susceptibility to injuries due to overload (Pelletier and Martel-Pelletier, 1993). Thus, the viscous and elastic properties of the synovial fluid due to the AH exert a role in the healthy and pathological articulation.

CONCLUSION

The knowledge of the cartilage physiology and the osteoarthrosis pathophysiology will help orthopedists to act in the prevention and early treatment of the disease consciously.

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Publication Dates

• Publication in this collection
  22 May 2007
• Date of issue
  June 2000