Effects of lysosomal enzymes on the type of collagen synthesized by bovine articular cartilage

Bovine articular cartilage normally synthesizes a collagen containing three identical α-chains. After pre-incubation with rat liver lysosomal enzymes, it begins to synthesize significant amounts of the more ubiquitous collagen of the (α₁)₂α₂ type. Since lysosomes are increased in osteoarthritis, it is possible that the abnormal biosynthetic patterns exhibited by cells in areas of degeneration are caused by such enzymes.Articular cartilage is an avascular tissue with very low cell density, composed primarily of extracellular substances such as collagen, proteoglycans, and glycoproteins. The structural integrity of this tissue depends on the relative proportion, nature, and structural organization of these components. Until recently, the destruction of cartilage seen in osteoarthritis was considered to result from a “wear and tear” process. This concept is not substantiated by recent ultrastructural and biochemical findings. Cellular activity in the involved areas leads to enlarged clones of chondrocytes containing increased numbers of intracellular organelles reflecting synthetic and secretory activity (1). There is an inverse correlation between the severity of the degenerative changes and the glycosaminoglycan content of the tissue (2–7). On the other hand, radioactive sulfate incorporation increases in osteoarthritis, an indication of the attempts made by the cells involved to repair the lesion (2). The nature of the proteoglycans synthesized under these conditions (less keratan sulfate and more chondroitin-4-sulfate) reflect the behaviour of immature chondroblasts (3–8). Lysosomal proteases have been associated with the degradation of the matrix (9–12). Cathepsin-D and a neutral protease which degrade proteoglycans at pH 5.0 and 7.0 respectively are considerably increased in early osteoarthritic lesions (13–15). Although the collagen content of cartilage does not change in osteoarthritis, qualitative differences may exist. Recently, we have shown that whereas normal human cartilage synthesizes only cartilage type collagen or (α₁-Type II)₃, osteoarthritic cartilage synthesizes in addition significant amounts of (α₁)₂α₂ collagen (skin type) (16). Articular cartilage collagen is quite different from other ubiquitous forms of mammalian collagens. In addition to containing three identical α-chains, it has four to five times more hydroxylysine and glycosidically associated carbohydrate than collagen from other tissues (17). It is quite possible that the abnormal collagen deposited by the cells at the site of degeneration may give rise to a mechanically weaker structure and lead to a loss of cartilage. While attempting to elucidate the mechanism underlying this abnormal metabolic pattern, it became apparent that lysosomal enzymes can alter the function of normal cartilage cells causing them to synthesize non-specific collagen molecules.