Abnormal expression of chondroitin sulphate N-acetylgalactosaminyltransferase 1 and Hapln-1 in cartilage with Kashin–Beck disease and primary osteoarthritis

Abstract

PurposeKashin-Beck disease (KBD) is an endemic degenerative osteoarthritis associated with extracellular matrix degradation. The aim of this investigation was to evaluate the role of targeting genes in the pathogenesis of KBD and primary osteoarthritis (OA) involved in extracellular matrix degradation.MethodsAgilent 44 K human whole-genome oligonucleotide microarrays were used to detect the gene expression in KBD and OA cartilage. The mRNA and protein expressions of CSGalNAcT-1 and Hapln-1 in chondrocytes were verified by reverse transcription polymerase chain reaction (RT-PCR) and western blot, and their expression in cartilage were verified with immunocytochemical analysis. Meanwhile, CSGalNAcT-1 and Hapln-1 protein levels in the selenium intervention group of KBD with different concentrations (0.25, 0.1and 0.05 μg/ml) were detected by western blot.ResultsCSGalNAcT-1 and Hapln-1 were down-regulated in KBD and OA at both mRNA and protein levels, and were increased in Se(Selenium) groups compared to KBD free-Se group. However, Wnt 3a, β-catenin and Runx-2 were up-regulated in OA and KBD at protein levels. Additionally, immunohistochemical staining showed that CSGalNAcT-1 and Hapln-1 were reduced in all zones of KBD and OA articular cartilage, but not significantly reduced in the up zone of OA articular cartilage.ConclusionsThe CSGalNAcT-1 and Hapln-1 were down-regulated in both KBD and OA cartilage. CSGalNAcT-1 may be involved in the damage of articular cartilage of KBD and OA by regulating Hapln-1 in the Wnt/β-catenin signalling pathway. It was indicated that CSGalNAcT-1 and Hapln-1 may play important roles in the pathogenesis of KBD and OA.

microRNA-140 Inhibits Inflammation and Stimulates Chondrogenesis in a Model of Interleukin 1β-induced Osteoarthritis

“…ACAN is the most important proteoglycan in articular cartilage while CSGALNACT1 is very important for synthesis of CS and normal development of articular cartilage in mice. 17,18,19 In mice, loss of NFATC1 and NFATC2 leads to OA. 20,21 HAT1 is an inhibitor of NFKB signaling.…”

“…In both these conditions CSGALNACT1 was considerably down-regulated. 19 In another study, CSGALNACT1 knockout mice were found to have thinner articular cartilage with more degraded ACAN compared with wildtype mice. 18 This suggests that upregulation of CSGALNACT1 following miR-140 transfection will be an important mechanisms for regeneration of the cartilage.…”

Copper, iron, and selenium dietary deficiencies negatively impact skeletal integrity: A review

“…This enzyme is critical in stabilizing the collagen matrix as it stabilizes the aggregation of aggrecan and hyaluronic acid. 52 Collectively, there appears to be decreased antioxidant activities and changes in expression of proteins involved with chondrocyte integrity in Kashin-Beck disease. Another study gives further insight as to the linkage between Kashin-Beck disease caused either by selenium deficiency or T2 toxin.…”

Total knee arthroplasty in elderly patients with severe Kashin-Beck disease of the knee

“…KBD is a disabling osteoarticular disease involving growth cartilage [25,26], usually leading to joint damage, pain, deformity and serious limitations in joint motion in the later stages of the disease. Currently, more than one million people, mostly adults, are affected by KBD in an endemic area that spans from southeastern Siberia, crosses northern China, and ends in central Tibet.…”