Chapter 3 Articular Cartilage and Intervertebral Disk

Structure and Function Articular cartilage is structurally well suited to support joint function: it provides a nearly frictionless interface between joint surfaces and protects underlying bones by redistributing loads. By bulk chemical analysis cartilage consists mainly of water (more than 70% of wet mass), proteoglycan (15% of wet mass), and collagen (15% of wet mass). More than 80% of the proteoglycan present is in the form of high-molecular-weight (more than 3.5 x 106 Da) aggregates of hyaluronic acid–linked aggrecan, a 250-kDa protein that is heavily populated with polyanionic sulfated glycosaminoglycans (keratan and chondroitin sulfate). In the matrix, aggrecan entrapment within a collagen fibril network results in densely packed negative charges, which are available to interact with water via hydrogen bonding. Electrostatic repulsion and a strong tendency to retain bound water enable cartilage to resist deformation under compression and to redistribute stresses by hydrostatic pressurization of the matrix. Histologic analysis reveals depth-dependent variation in cartilage matrix structure; four distinct zones (superficial, transitional, radial, calcified) can be distinguished based on differences in cell morphology, matrix composition, and collagen fibril orientation. These depth-dependent variations result in marked anisotropy and, as a result, chondrocytes experience different stresses depending on their location in the depth of the matrix. The superficial zone is relatively low in proteoglycan content compared with the deeper zones and, in contrast to deeper zones where collagen fibrils run perpendicular or orthogonal to the surface, the collagen network runs parallel to the surface. Thus, this zone is specialized to resist tensile stresses. Superficial zone chondrocytes are also somewhat distinct from cells in other zones: they are comparatively flat in shape and less rigid due to the absence of vimentin filaments, which enhance the stiffness of the cytoskeleton. These features appear to be an adaptation to the relatively higher strains experienced by these cells compared with cells lodged in the deeper zones where proteoglycan is more abundant. Superficial chondrocytes also secrete a specialized glycoprotein called lubricin (also known as superficial zone protein, or PRG4), which coats cartilage surfaces and lowers surface friction. Intra-articular injection of recombinant lubricin prevented cartilage degeneration in a rat meniscal tear model of osteoarthritis (OA), indicating that friction plays a role in cartilage degeneration in OA.1 The cartilage extracellular matrix (ECM) is thinly populated by chondrocytes, cells of mesenchymal lineage that are adapted for life in the demanding environment of the articular surface. Despite their low tissue density, articular chondrocytes exert a profound influence on cartilage matrix stability. Chondrocyte depletion is associated with aging and OA, and the prevention of chondrocyte death blocks matrix degeneration after cartilage injury. Chondrocytes maintain the ECM by actively synthesizing its components, but also contribute to matrix degradation by synthesizing matrix proteases. Disturbance in the balance between biosynthetic and degradative activities destabilizes the ECM and is a hallmark of OA. Cartilage is avascular and nourished only by way of synovial fluid at its surface and through subchondral bone at its base. Intratissue oxygen saturation is predictably low (2% to 10%), but chondrocytes tolerate such mild hypoxic conditions, relying for the most part on glycolysis for adenosine triphosphate (ATP) production. Presumably, in normal cartilage ATP is generated in sufficient quantity to meet demands for maintenance-level biosynthesis of proteoglycans and collagens. However, very low oxygen levels (less than 1%) inhibit glycolytic activity via negative feedback by Dr. Buckwalter or an immediate family members serves as a paid consultant for or is an employee of ISTO and Carbylan Bioscience and is a board member, owner, officer, or committee member of the American Orthopaedic Association. None of the following authors nor any immediate family member has received anything of value from or owns stock in a commercial company or institution related directly or indirectly to the subject of this chapter: Dr. Martin, Dr. Ramakrishnan, and Dr. Thedens.