Low selenium and T-2 toxin may be involved in the pathogenesis of Kashin-Beck disease by affecting AMPK/mTOR/ULK1 pathway mediated autophagy.

Kashin-Beck disease (KBD) is an endemic, environmentally associated cartilage disease. Previous studies have shown that the environmental suspected pathogenic factors of KBD, T-2 toxin and low selenium, are involved in the regulation of inflammation, oxidative stress and autophagy in some tissues and organs. In cartilage diseases, the level of cellular autophagy determines the fate of the chondrocytes. However, whether autophagy is involved in KBD cartilage lesions, and the role of low selenium and T-2 toxins in KBD cartilage injury and autophagy are still unclear. This work took the classical AMPK/mTOR/ULK1 autophagy regulatory pathway as the entry point to clarify the relationship between the environmental suspected pathogenic factors and chondrocyte autophagy. Transmission electron microscopy was used to observe the autophagy of chondrocytes in KBD patients. qRT-PCR and western blot were used to analyze the expression of AMPK/mTOR/ULK1 pathway and autophagy markers. The rat model of KBD was established by low selenium and T-2 toxin, the autophagy in rat cartilage was detected after 4- and 12-week interventions. Chondrocyte autophagy was found in KBD, and the AMPK/mTOR/ULK1 pathway was down-regulated. In the rat model, the pathway showed an up-regulated trend when low selenium and T-2 toxin, were treated for a short time or low concentration, and autophagy level increased. However, when low selenium and T-2 toxin were treated for a long time or at high concentrations, the pathway showed a down-regulated trend, and the autophagy level was reduced and even defective. In conclusion, in the process of KBD cartilage lesion, chondrocyte autophagy level may increase in the early stage, and decrease in the late stage with the progression of lesion. Low selenium and T-2 toxins may affect autophagy by AMPK/mTOR/ULK1 pathway.

A multi-scale elasto-plastic model of articular cartilage.

Collagen damage is one of the earliest signs of cartilage degeneration and the onset of osteoarthritis (OA), but the connection between the microscale damage and macroscale tissue function is unclear. We argue that a multiscale model can help elucidate the biochemical and mechanical underpinnings of OA by connecting the microscale defects in collagen fibrils to the macroscopic cartilage mechanics. We investigated this connection using a multiscale fibril reinforced hyperelastoplastic (MFRHEP) model that accounts for the structural architecture of the soft tissue, starting from tropocollagen molecules that form fibrils, and moving to the complete soft tissue. This model was driven by reported experimental data from unconfined compression testing of cartilage. The model successfully described the observed transient response of the articular cartilage in unconfined and indentation tests with low and high loading rates. We used this model to understand damage initiation and propagation as a function of the cross-link density between tropocollagen molecules. This approach appeared to provide a realistic simulation of damage when compared with certain published studies. The current construct presents the first attempt to express the aggregate cartilage damage in terms of the cross-link density at the microfibril level.