Osteoarthritis is a degenerative disease affecting a large proportion of the population. Recently, there has been renewed interest in the use of neutraceuticals (such as glucosamine) for the treatment of symptomatic pain and pathology in arthritic joints. However, little research has been carried out to assess the biochemical mechanisms by which glucosamine imparts its effects on the disease process. Biochemically, an early change in cartilage metabolism is a loss of the large aggregating proteoglycan, named aggrecan. Functionally, this loss results in a decreased capacity for the tissue to sustain mechanical loading and eventually leads to cartilage destruction and a painful joint. The enzymes responsible for the loss of aggrecan from the tissue are commonly referred to as the aggrecanases and are members of the A Disintegrin And Metalloproteinase with ThromboSpondin motifs (ADAMTS) family of enzymes. Degradation of aggrecan by the aggrecanases can be detected using a specific neo-epitope monoclonal antibody BC-3.1 Model systems using cartilage explant cultures that mimic the degradative processes seen in osteoarthritis have been developed in which cytokines such as IL-1 are used to initiate the catabolic processes leading to cartilage degradation. In this study, we have investigated the effects of pretreatment of articular cartilage explant cultures with preparations of chemically modified glucosamine on their ability to inhibit the release of aggrecan following treatment with IL-1. Initial experiments have shown that glucosamine hydrochloride was unable to inhibit the release of aggrecan from explant cultures; however, a modified glucosamine was able to inhibit the release of aggrecan to that of control culture levels that were not treated with either glucosamine or IL-1. These data suggest a role for chemically modified glucosamine in the treatment of arthritic disease and help explain the potential role of the dietary ingestion of glucosamine and its beneficial effects with arthritis patients.
Reference
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