An in vitro model to study cartilage metabolism in Kashin-Beck disease
Hodgson, Paul David
Kashin-Beck disease is endemic chronic degenerative osteoarthropathy whose main pathological changes occur in the growth plate and articular cartilage of human limbs and joints, where it is manifest as cartilage degeneration and necrosis. The effects of the disease on the growth plate therefore alter growth in children and can lead to growth arrest (short stature and limbs) and developmental deformities (crooked joints). In adulthood patients present with pain and deformity commonly affecting the hand, wrist, elbow, knee and ankle with radiological features and joint pattern involvement similar to those seen in rheumatoid arthritis. Past and current research suggests that Kashin-Beck disease, with its endemic geographical distribution in China and Tibet, is due to the combined presence of fungal mycotoxins (found on the stored food ingested by affected populations) and a regional selenium deficiency in the environment providing local food sources. This evidence is supported by the correlation between the geographical occurrence of these 2 factors and the incidence of Kashin-Beck disease. The objective of this study was to develop and in vitro cartilage culture system to mimic the changes seen in Kashin-Beck disease and thus determine the effects different sources of selenium, in the presence or absence of Nivalenol, had on cartilage neograft metabolism. Our hypothesis was that growth and metabolism of cartilage will be affected by exposure to either selenium or the mycotoxin Nivalenol or both in combination and these effects will mimic those found in Kashin-Beck disease. Collectively, the results of this study suggest that Nivalenol is the major contributor to cartilage pathology in this in vitro system that mimics Kashin-Beck disease, and that these deleterious effects are largely independent from selenium supplementation.