The molecular mechanism study of COMP involved in the articular cartilage damage of Kashin-Beck disease

Abstract

Aims Kashin-Beck disease (KBD) is a kind of chronic osteochondropathy, thought to be caused by environmental risk factors such as T-2 toxin. However, the exact aetiology of KBD remains unclear. In this study, we explored the functional relevance and biological mechanism of cartilage oligosaccharide matrix protein (COMP) in the articular cartilage damage of KBD. Methods The articular cartilage specimens were collected from five KBD patients and five control subjects for cell culture. The messenger RNA (mRNA) and protein expression levels were detected by quantitative reverse transcription PCR (qRT-PCR) and western blot. The survival rate of C28/I2 chondrocyte cell line was detected by MTT assay after T-2 toxin intervention. The cell viability and mRNA expression levels of apoptosis related genes between COMP-overexpression groups and control groups were examined after cell transfection. Results The mRNA and protein expression levels of COMP were significantly lower in KBD chondrocytes than control chondrocytes. After the T-2 toxin intervention, the COMP mRNA expression of C28/I2 chondrocyte reduced and the protein level of COMP in three intervention groups was significantly lower than in the control group. MTT assay showed that the survival rate of COMP overexpression KBD chondrocytes were notably higher than in the blank control group. The mRNA expression levels of Survivin, SOX9, Caspase-3, and type II collagen were also significantly different among COMP overexpression, negative control, and blank control groups. Conclusion Our study results confirmed the functional relevance of COMP with KBD. COMP may play an important role in the excessive chondrocytes apoptosis of KBD patients. Cite this article: Bone Joint Res 2020;9(9):578–586.

Cartilage Oligomeric Matrix Protein, Diseases, and Therapeutic Opportunities

“…However, quantitative proteomic analysis revealed an elevated COMP level in AF of IVDD patients [ 91 ]. COMP mRNA and protein expression levels are much lower in the chondrocytes from Kaschin–Beck disease (KBD) patients [ 92 ]. When COMP is overexpressed, Survivin and SOX9 mRNA expression levels in KBD chondrocytes are significantly higher than in the control group, suggesting that COMP may play a role in the excessive KBD chondrocyte apoptosis by reducing Survivin and SOX9 expression [ 92 ].…”

Comprehensive expression profiles of mRNAs, lncRNAs and miRNAs in Kashin-Beck disease identified by RNA-sequencing

“…In addition, the formation of chondrocyte clusters and osteophytes has also been deemed to be pathological changes in KBD. 5 Three primary etiologies in environmental factors have prevailed the past few decades, including selenium deficiency, cereal contamination by mycotoxin-producing fungi and high humic acid levels in drinking water. 6 However, in terms of genetic factors, the underlying molecular mechanism involved in the pathogenesis of KBD has not been completely elucidated to date.…”