FULVIC-ACID SUPPLEMENTATION AND SELENIUM DEFICIENCY DISTURB THE STRUCTURAL INTEGRITY OF MOUSE SKELETAL TISSUE - AN ANIMAL-MODEL TO STUDY THE MOLECULAR DEFECTS OF KASHIN-BECK DISEASE

High concentrations of fulvic acid and selenium deficiency are the main causative factors of Kashin-Beck disease, an endemic, chronic and degenerative osteoarticular disorder found in China. In the search for an animal model of this disease, mice were exposed to these pathogenetic conditions for two generations and the collagen types from skin, bone and cartilage were analysed. The growth of the treated mice was slightly retarded, and the rate of reproduction was lower in animals maintained on a fulvic acid-supplemented and/or selenium-deficient diet. Irregular bone formation was seen by radiography and morphometry. Biochemical analysis indicated that lysine residues in collagen I from bone and in collagen II from cartilage were overmodified. The values of Hyl/(Hyl+Lys) in bone collagen alpha1(I) chains from treated mice were about 0.434-0.484, i.e. substantially higher than that of the control (0.277). The values of this parameter for collagen II were 0.482 for control and 0.546-0.566 for treated mice. The melting temperature of collagen I from bones of treated mice was 1-degrees-C lower than that of control collagen, indicating decreased thermal stability. The breakage point of the tibiae of treated mice occurred at a lower preload force than for controls. suggesting that the overmodified and thermally less stable collagen molecules are causally related to a lower mechanical strength of bones.