Background:

Kashin Beck Disease (KBD) is a chronic joint disease with deteriorated health conditions causing major functional limitation and disability. The pathogenesis of KBD has not yet been fully clarified, but the general presumption is that the etiology should bemulti-factorial due to a combination of nutritional, environmental, immunological, genetic, and infectious factors. Selenium deficiency presents in KBD endemic rural areas. Evidence suggest that KBD maybe caused by mycotoxins, such as T-2 toxin, by which the proteoglycan synthesis is disturbed, leading to severe cartilage damage.Our hypothesis is that T-2 toxin contamination in food under selenium-deficient conditionsmay be included in the etiological factors contributing to the occurrence of KBD. In this study, we employed a rat model of KBD by employing T-2 toxin administration in animals maintained with a low selenium diet.

The epiphyseal plate of cartilage from KBD patient shows necrosis and apoptosis in the hypertrophic layer near the adjacent subchondral bone. However, the mechanism-underlying the perpetuation of cartilage destruction is still unknown. Cytokines are thought to play an important role in articular cartilage degeneration. Chondrocytes expressing proinflammatory cytokines are capable of modulating a local inflammatory cascade in articular cartilage, which maypotentially lead to focal degradation and OA. Our hypothesis is, therefore, that IL-1β, TNF-α, and IL-6 arekey mediators of particular cartilage destruction in eastablished rat model of KBD.

Objective and methods:

To compare and investigate the possible role of inflammatory mediators, such as IL-6，IL-1β and TNF-αin KBD children andKBD rats fed with T-2 toxin under a selenium deficiency conditions, Sprague–Dawleyrats were administerd a selenium-deficient diet for 4 weeks prior to their exposure to T-2 toxin for 4 weeks. The morphology of joint cartilages of KBD children andKBD and control rats were examined by light microscopy and the expression of proteoglycans was determined by histochemical staining. The serum levels of IL-6, IL-1β and TNF-α were determined by ELISA. IL-6, IL-1β and TNF-αin the knee joints of rats and metacarpophalangeal joints of KBD children were visualized by immunohistochemistry, and their mRNA levels in the cartilageof rats were detected by real-time RT-PCR.

Our basic findings are:

  1. The levels of IL-6 in serum were significantly elevated in rats fed withselenium-deficient, T-2 toxin, and T-2 toxin plus selenium-deficient diets compared to those in the normal diet group, while the levels of IL-1β and TNF-α in serumwere significantly increased only in theT-2 toxin plus selenium-deficient dietgroup.
  2. Staining forIL-6, IL-1β and TNF-αincartilages of KBD childrenwas significantly higher than that in controls.
  3. IL-6, IL-1β and TNF-α preotein in cartilage were significantly higher in rats feddiets of T-2 toxin alone and T-2 toxin plus selenium-deficiency than that in rats fed normal orselenium-deficient diet.
  4. IL-6, IL-1β and TNF-αmRNA levelsin cartilages were significantly higher in rats feddiets of T-2 toxin alone and T-2 toxin plus selenium-deficiency than that in rats fed normal orselenium-deficient diet.

Conclusion:

In this study, we have demonstrated that chondral destructionpresents in the deep zone of articular cartilage associated with high serumlevels of IL-1β, TNF-α, and IL-6and increased expression in cartilageobtained fromKBD children and rats with selenium-deficient nutritionorT-2 toxin treatment.T-2 toxin under a selenium-deficiency nutritional status induces increases inIL-6、IL-1β and TNF-αin serum and cartilages,which may account for the pathological mechanism underlying the cartilage damage in KBD.