Decreased Expression of CHST-12, CHST-13, and UST in the Proximal Interphalangeal Joint Cartilage of School-Age Children with Kashin–Beck Disease: an Endemic Osteoarthritis in China Caused by Selenium Deficiency
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The objective of this study is to investigate changes in the expression of enzymes involved in chondroitin sulfate (CS) sulfation in distal articular surface of proximal interphalangeal joint isolated from school-age children patients with Kashin–Beck disease (KBD), using normal children as controls. Articular cartilage samples were collected from four normal and four KBD children (7–12 years old), and these children were assigned to control and KBD groups. Hematoxylin and eosin (H&E), toluidine blue (TB), and immunohistochemical (IHC) stainings were utilized to evaluate changes in joint pathology and expression of enzymes involved in CS sulfation, including carbohydrate sulfotransferase 12 (CHST-12), carbohydrate sulfotransferase 13 (CHST-13), and uronyl 2-O-sulfotransferase (UST). The correspondence results were examined by semi-quantitative analysis. Compared with the control group, the KBD group showed the following: a significant decrease of total chondrocytes in superficial, middle, and deep layers and deposition of sulfated glycosaminoglycans in extracellular matrix of KBD cartilage were observed; positive staining chondrocytes of CHST-12, CHST-13, and UST were significantly less in superficial zone of KBD cartilage; and CHST-13 positive staining chondrocytes was reduced in deep zone of KBD cartilage. In contrast, the positive staining rates of CHST-12, CHST-13, and UST in KBD were significantly higher than those in the control group. The decreased expression of these enzymes and the physiologic compensatory reaction may be the signs of early-stage KBD. The alterations of CS structure modifying sulfotransferases in finger articular cartilage might play an important role in the onset and pathogenesis of school-age KBD children.
KeywordsKashin–Beck disease Selenium deficiency Child cartilage Chondroitin sulfate Sulfation Sulfotransferases
We thank senior technician Zengtie Zhang and Jian Lei from the Public Health Department of Xian Jiaotong University for his support and cooperation in the collection of cartilage specimens and staining.
This study was supported by the National Natural Science Foundation of China (81402639, 81872567) and Shenzhen Science and Technology Project (JCYJ20170816100755047).
Compliance with Ethical Standards
All human experimental procedures followed the protocols approved by the Medical Research Ethics Committee at Xi’an Jiaotong University and were in accordance with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. All the KBD and normal donors or their guardians had provided a written informed consent for the study participation and publication of their individual clinical details and images
Conflict of Interest
The authors declare that they have no conflicts of interest. The authors’ affiliations are shown on the cover page. The authors have sole responsibility for the writing and content of the paper.
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