Dietary Glucosamine: Does it Affect Cartilage Function?
The claim is that dietary glucosamine enhances the ability of cartilage cells, the chondrocytes, to produce the major extracellular matrix molecules responsible for maintaining cartilage function. Hyaluronan and proteoglycans molecules provide cartilage with its shock-absorbing ability to withstand compressive loads. When their synthesis is compromised, the tissue can become damaged, and degenerative processes can begin to erode the matrix with eventual loss of tissue function. This leads to the clinical manifestations of osteoarthritis, joint pain and loss of motion.
In a project funded by the Arthritis Foundation, we have developed a model system for studying the response of chondrocytes in culture to exposure to glucosamine. Our question is whether oral glucosamine can increase the synthesis of the extracellular matrix molecules of cartilage and partially restore tissue function.
Preliminary experiments have explored the effect of glucosamine at concentrations that would be expected to reach the articular joint after ingestion of a dose recommended by the vendors and in the presence of near physiological levels of glucose. Our results suggest that the glucosamine in these conditions has little effect on the synthesis of hyaluronan or proteoglycans by the chondrocytes, and that the major source for the glucosamine used by the cells to synthesize these molecules comes from glucose in the medium.
Replicating in vivo Conditions in the Laboratory
A major difficulty in developing a culture model that mimics conditions experienced in actual tissue is the inability to maintain near-normal physiological levels of glucose. In the chondrocyte cultures we use, the cells rapidly deplete glucose in the medium. One approach has been to replenish glucose periodically by adding small aliquots of a concentrated glucose solution. Another approach is a continuous flow system coupled with monitoring the medium that perfuses the tissue. In this system, substances that enter the system (glucose, glucosamine, growth factors, etc.) can be precisely controlled, and changes can be measured once they exit. In addition, the amounts of the relevant matrix molecules that are synthesized and either released into the medium or retained in the culture matrix can be measured as a function of time.
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