Proteoglycans are complex macromolecules that consist of a protein core with covalently bound polysaccharide (glycosaminoglycan) chains (Fig. 3).

Figure 3 Schematic diagram of a proteoglycan. The protein core has several globular domains (G1, G2, and G3), with other regions containing the keratan sulfate and chondroitin sulfate glycosaminoglycan chains. The N-terminal G1 domain is able to bind specifically to hyaluronate.This binding is stabilized by link protein. (Reproduced from Mankin HJ, Mow VC, Buckwalter JA, Iannotti JP, Ratcliffe A: Articular cartilage structure, composition, and function, in Buckwalter JA, EinhornTA, Simon SR (eds): Orthopaedic Basic Science: Biology and Biomechanics of the Musculoskeletal System, ed 2. Rosemont, IL, American Academy of Orthopaedic Surgeons, 2000, pp 443-470.)


Glycosaminoglycans consist of long-chain, unbranched, repeating disaccharide units. Three major types have been found in cartilage: (1) chondroitin sulfate (found in two isomeric forms, chondroitin 4-sulfate and chondroitin 6-sulfate); (2) keratan sulfate; and (3) dermatan sulfate. The chondroitin sulfates are the most prevalent glycosaminoglycans in cartilage. They account for 55% to 90% of the total population, depending principally on the age of the subject. Each chain is composed of 25 to 30 repeating disaccharide units. The keratan sulfate constituent of articular cartilage resides primarily within the large, aggregating proteoglycan. Hyaluronate is also a glycosaminoglycan, but unlike those described above, it is not sulfated. A further distinguishing feature of hyaluronate is that it is not bound to a protein core, and, therefore, is not part of a proteoglycan. Approximately 80% to 90% of all proteoglycans in cartilage are of the large, aggregating type, called aggrecans (Fig. 4).

Figure 4 Electron micrograph of bovine articular cartilage proteoglycan aggregates from skeletally immature calf.The aggregates consist of a central hyaluronic acid filament and multiple attached monomers. (Reproduced with permission from Buckwalter JA, Kuettner KE, Thonar EJ: Age-related changes in articular cartilage proteoglycans: Electron microscopic studies. J Orthop Res 1985;3:251– 257.)

They consist of a long, extended protein core with up to 100 chondroitin sulfate and 50 keratan sulfate glycosaminoglycan chains covalently bound to the protein core. In young individuals, the concentration of keratan sulfate is relatively low, and chondroitin 4-sulfate is the predominant form of chondroitin sulfate. With increasing age, the concentration of keratan sulfate increases, and chondroitin 6-sulfate becomes the predominant isomeric form of chondroitin sulfate.