Down-regulation of decorin expression in chondronecrosis of Kaschin-Beck disease

Abstract

Objective To investigate the expression of Decorin in Kaschin-Beck disease (KBD) cartilage as well as in a KBD model of T-2 toxin under selenium deficient conditions and in human chondrocyte in vitro in order to determine a possible mechanism underlying KBD. Methods Immunohistochemical staining of Decorin was performed on sections of human phalanges of hands from normal (samples from 5 normal children, traffic accident or operation) and KBD children (samples from children with KBD), and 32 Sprague-Dawley rats were divided into two groups according to random number table method: normal diet group (n = 16) and selenium-deficient group (n = 16). The selenium level in normal diet was 101.5 μg/kg, and in selenium-deficient diet was 1.1 μg/kg, feeding for 30 days with selenium-deficient or normal diet, respectively. After confirmed the selenium status, normal diet group was further subdivided into 2 sub-groups: normal diet group (n = 8) and normal diet plus low T-2 toxin group (n = 8), and selenium-deficient group was subdivided into 2 sub-groups: selenium-deficient diet group (n = 8) and selenium-deficient diet plus T-2 toxin group (n = 8). T-2 toxin of 100 μg/kg · BW/day was administered by intragastric administration for 30 days. Then the rats were sacrificed, and their knee joints were processed for histopathological evaluation. Decorin localization in cartilages was performed by immunohistochemistry. Human chondrocyte C28/I2 was cultured and exposed to T-2 toxin(0, 1, 6, 12 μg/L) for 72 h. Real-time PCR was performed to detected Decorin mRNA expression. Results The percentages of chondrocyte staining for Decorin in the superficial zones, middle zones and deep zones of KBD samples [(1.75 ± 0.95)%, (8.92 ± 3.45)%, (0.00 ± 0.00)%] were significantly lower than those in controls [(21.27 ± 3.44)%, (78.70 ± 8.82)%, (93.12 ± 6.99)%, t = 11.76, 12.87, 31.09, all P < 0.05]. The percentages of chondrocyte staining for Decorin staining in rats fed with selenium-deficient diets plus T-2 toxin [(19.33 ± 2.82)%] were significantly lower than those in the normal, selenium-deficient diet and normal diets plus T-2 toxin [(62.67 ± 5.33)%, (53.17 ± 2.41)%, (34.50 ± 2.64)%, all P < 0.05]. When the concentration of selenium was 0 mg/L, the level of Decorin mRNA expression in control group (1.00 ± 0.00) was significantly higher than those of 6, 12 μg/L T-2 toxin groups (0.38 ± 0.01, 0.26 ± 0.03, all P < 0.05); when 0.1 mg/L of selenium was added, Decorin expression in T-2 toxin (0, 6, 12 μg/L) plus selenium groups (1.53 ± 0.06, 1.92 ± 0.04, 2.50 ± 0.01 )were higher than those of the same dose of T-2 toxin group (1.00 ± 0.00, 1.00 ± 0.00, 1.00 ± 0.00, all P < 0.05). Conclusions Decreased Decorin staining intensity is observed in cartilage of KBD as well as in KBD model exposed to T-2 toxin under selenium deficient conditions; T-2 toxin has reduced their mRNA expressions in C28/I2 cells in a dose-dependent pattern. Selenium could partly block the inhibitory effect of T-2 toxin. Decorin has an important role in death of chondrocytes and degradation of cartilage matrix. Key words: Kaschin-Beck disease; Decorin; T-2 toxin