The Importance of Se-Related Genes in the Chondrocyte of Kashin-Beck Disease Revealed by Whole Genomic Microarray and Network Analysis.

Kashin-Beck disease (KBD) is an endemic, chronic, and degenerative osteoarthropathy. Selenium (Se) deficiency plays important role in the pathogenesis of KBD. We aimed to screen Se-related gene from chondrocytes of patients with KBD. Whole-genome oligonucleotide microarrays were used to detect differentially expressed genes. qRT-PCR was used to confirm the microarray results. Comparative Toxicogenomics Database (CTD) was used to screen Se-related genes from differentially expressed genes. Gene Ontology (GO) classifications and network analysis of Se-related genes were constituted by STRING online system. Three hundred ninety-nine differentially expressed genes were obtained from microarray. Among them, 54 Se-related genes were identified by CTD. The qRT-PCR validation showed that four genes expressed similarly with the ones in the microarray transcriptional profiles. The Se-related genes were categorized into 6 cellular components, 8 molecular functions, 44 biological processes, 10 pathways, and 1 network by STRING. The Se-related gene insulin-like growth factor binding protein 2 (IGFBP2), insulin-like growth factor binding protein 3 (IGFBP3), interleukin 6 (IL6), BCL2, apoptosis regulator (BCL2), and BCL2-associated X, apoptosis regulator (BAX), which involved in many molecular functions, biological processes, and apoptosis pathway may play important roles in the pathogenesis of KBD.

Associations Between Selenium Content in Hair and Kashin-Beck Disease/Keshan Disease in Children in Northwestern China: a Prospective Cohort Study.

The objective of this study was to investigate the relationship between selenium content in hair and the incidence of Kashin-Beck disease (KBD) and Keshan disease (KD) in China. A prospective cohort study was conducted among children aged 5-12 years with different levels of low-selenium (group 1, Se ≤ 110 ng/g; group 2, 110 < Se ≤ 150 ng/g; and group 3, 150 < Se ≤ 200 ng/g) or selenium-supplemented (group 4, Se > 200 ng/g) exposure. A person-years approach was used to calculate the incidence and rate of positive clinical signs. Relative risk (RR), attributable risk, and etiologic fraction were used to determine the strength of association between selenium and disease incidence. Seven new KBD cases were diagnosed during 3-year follow-up. Positive clinical signs of KBD were found in 17.78 (95% confidence interval [CI] 14.27-21.29) cases per 100 person-years in group 1, 13.28 (9.82-16.74) in group 2, 12.95 (9.34-16.56) in group 3, and 8.18 (5.50-10.85) in group 4. Compared with group 4, the RR (95% CI) of groups 1, 2, and 3 were 2.17 (1.48-3.19), 1.62 (1.07-2.47), and 1.58 (1.03-2.43), respectively. Positive clinical signs of KD were 25.90 (18.62-33.18) cases per 100 person-years in group 1, 5.66 (1.26-10.06) in group 2, 4.60 (0.20-9.00) in group 3, and 14.62 (8.54-20.69) in group 4. Compared with group 4, the RR (95% CI) were 1.77 (1.07-2.93), 0.39 (0.16-0.93), and 0.31 (0.11-0.89), respectively. In children, the onset of KBD was negatively correlated with selenium content within a certain range. However, there may be a U-shaped association between selenium content and KD in children.

The roles of selenium, insulin-like growth factor binding protein 2 and suppressor of cytokine signaling 3 in the pathogenesis of Kashin-Beck disease.

We aimed to verify the levels of IGFBP2 and SOCS3 in cartilage and chondrocytes of Kashin-Beck disease (KBD) patients and the effects of different selenium concentrations on the protein expression levels. Chondrocytes were cultured with sodium selenite in vitro. Immunohistochemistry and western blotting were used to verify the protein expressions. IGFBP2 and SOCS3 were up-regulated in KBD chondrocytes and decreased with increasing selenium concentrations. IGFBP2 expressed highest in the middle zone of KBD cartilage, SOCS3 expressed higher in the middle and deep zone. IGFBP2 and SOCS3 may be the biomarkers for KBD diagnosis and evaluating the effect of selenium supplement.