The complexity of understanding osteoarthritis is well illustrated by considering the conflicting conclusions that can be drawn from clinical and laboratory reports on the relative influence of mechanical factors on the progression of degenerative changes to the articular cartilage at the knee. For example, experimental and theoretical studies suggest that load can produce an adaptive response (thickening, enhanced mechanical properties, etc.) (Carter et al., 1998; Carter and Wong, 2003) of cartilage. In contrast, clinical studies report that patients with knee osteoarthritis and higher loads at the knee during walking have a more rapid rate of cartilage breakdown than patients with lower loads (Miyazaki et al., 2002; Prodromos et al., 1985). Clearly, the conclusion that cartilage responds positively to increased load is in conflict with clinical observations that increased load stimulates more rapid breakdown of articular cartilage. As will be discussed later, it appears that the cartilage response to load is dependent on the health of the cartilage.
In vivo studies can provide an integrated approach that consolidates the multiple pathways associated with the cause and progression of osteoarthritis. Gait analysis, quantitative magnetic resonance imaging (MRI), and assays of biomarkers provide methods to evaluate a framework for understanding the interrelationship between the factors that influence the progression of osteoarthritis (see Figure 77.1).
The purpose of this chapter is to describe an integrated view of the in vivo pathomechanics of osteoarthritis associated with aging. The material is based on studies of assays of biomarkers, cartilage morphology (quantitative MRI), and human function (gait analysis).
Cartilage Mechanobiology, Osteoarthritis, and Aging
The structure and function of articular cartilage are maintained by the metabolic activity of chondrocytes, the cells in cartilage. The chondrocytes are embedded in a highly structured avascular extracellular matrix. The extracellular matrix is made up of structural proteins including collagen, proteoglycans, other proteins, peptides, and water.
Type II collagen fibrils form a network within the tissue with different primary fiber orientation in the deep zone (closest to bone), transitional zone, middle zone, and superficial zone (closest to cartilage surface) (see Figure 77.2). The zones contain different collagen organization as well as different amounts of proteoglycans. The collagen fibers are responsible for the tensile strength of cartilage and are surrounded by the matrix that primarily consists of water. Pro-teoglycans are responsible for the compressive strength, are arranged within the collagen network, and attract water. Other proteins and peptides, including growth
Figure 77.2 Cartilage can be organized into four zones from a functional viewpoint.
The Superficial Tangential Zone is the thinnest layer, with the highest content of collagen and the lowest concentration of proteoglycans; contains flat chondrocytes and collagen fibers arranged tangentially to the articular surface; has greatest ability to resist shear stresses and serves as a gliding surface for the joint; limits passage of large molecules between synovial fluid and cartilage; the first to show changes of osteoarthritis. The Transition Zone is composed almost entirely of proteoglycans and spherical chondrocytes; this zone involves the transition between the shearing forces of the surface layer to compression forces in the deeper cartilage layers.
The Deep Zone is the largest part of the articular cartilage. It contains elongated chondrocytes and collagen fibers aligned perpendicular to the subchondral plate; this zone distributes loads and resists compression.
The Calcified Cartilage Zone separates hyaline cartilage from subchondral bone; contains mainly type X collagen in the calcified cartilage layer and in hypertrophic zone of the growth plate; capillary buds penetrate the layer of calcified cartilage as osteoarthritis progresses.
factors, cytokines, and metalloproteinases, are responsible for tissue growth, communication between chondrocytes, and regulation of anabolic and catabolic processes.
The early stages of osteoarthritis are associated with fraying and fibrillation of the superficial layer of cartilage (see Figure 77.3) and there is a reduction of chondrocytes in superficial zones. The cartilage matrix loses proteoglycans, and in the later stages capillary buds penetrate the layer of calcified cartilage. The pain associated with osteoarthritis is associated with synovial hypertrophy creating increased intra-articular pressure and producing joint pain.
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