Changes in the Extracellular Matrix of Articular Cartilage in Human Osteoarthritis
Articular cartilage is carefully organized to provide an articulating surface that provides almost frictionless movement and the ability to absorb and dissipate compressive load and resist tensile forces. The cartilage is organized into zones, the structures of which reflect the mechanical forces acting upon the cartilage. Type II collagen, together with type IX and type XI collagens, forms a fibrillar network throughout the matrix which is secreted by the chondrocytes. The large aggregating proteoglycans and the smaller proteoglycans interact directly or indirectly with this fibrillar network. The collagen and the proteoglycans can be degraded by metalloproteinases produced by the chondrocytes. In osteoarthritis, early damage to the collagen fibrillar network is seen at the articular surface and in the upper mid-zone. It is accompanied by a local loss of the large aggregating proteoglycan and small proteoglycans. Large proteoglycans exhibit degradative changes at this stage. With further progression of disease, fibrillation of cartilage occurs and proteoglycans are lost and replaced by larger more intact molecules with different glycosaminoglycan chains. Collagen damage now extends throughout the cartilage. There are also significant changes in the organization of the small proteoglycans, decorin and biglycan, in the osteoarthritic cartilage. Overall, a major reorganization of proteoglycans occurs with net collagen damage. We now know which proteases degrade both the collagen and the proteoglycan and how their synthesis, secretion and activity may be stimulated. The arthritis probably results from a mechanical stimulation of protease activity with impaired collagen fibril assembly although proteoglycan synthesis continues actively. Thus, the key to the survival of the cartillage is the protection and preservation from damage of the inact type II collagen fibrillar network. Clearly, there is no evidence of impaired proteoglycan synthesis, but retention of proteoglycans is prevented when collagen is damaged.
Key wordsCartilage Osteoarthritis Prntenalvrans Collagen Proteinases
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