CircVCAN regulates the proliferation and apoptosis of osteoarthritis chondrocyte through NF-κB signaling pathway

H.-R. Ma, W.-B. Mu, K.-Y. Zhang, H.-K. Zhou, R.-D. Jiang, L. Cao

State Key Laboratory of Pathogenesis, Prevention and Treatment of High Incidence Diseases in Central Asia, Clinical Medicine Institute, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, P.R. China. xjbone@sina.com

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• Orthopedics

OBJECTIVE: Osteoarthritis is one of the chronic diseases with a high incidence. CircRNA is a circular non-coding RNA. Studies show that CircRNA is closely relevant to the pathogenesis of OA chondrocytes. However, the specific principle is still unclear.

PATIENTS AND METHODS: 38 patients with OA tissues and 38 patients with normal knee cartilage in our hospital were selected, respectively. The mRNA expression levels of CircVCAN were measured by quantificational real-time polymerase chain reaction (qRT-PCR). Cell proliferation was detected by the Cell Counting Kit (CCK8). Cell cycle and apoptosis of OA chondrocytes were measured by flow cytometry. qRT-PCR and western blot were used to detect PCNA, p50, p52, p65 mRNA and protein expression levels.

RESULTS: CircVCAN was highly expressed in OA tissues and OA chondrocytes. Cell proliferation and PCNA expression levels decreased significantly after transfection with si-CircVCAN in OA-chondrocytes. However, there was a significant increase on OA chondrocytes after transfection with LV-CircVCAN. Compared with the si-NC group, the apoptosis rate of OA chondrocytes was significantly increased after transfection with si-CircVCAN. The proportion of G0/G1 phase in the cell cycle was significantly reduced and the proportion of S phase was significantly increased. On the contrary, the apoptosis rate was significantly reduced after transfection with LV-CircVCAN. The proportion of G0/G1 phase in the cell cycle was significantly increased and the proportion of S phase was significantly reduced. The mRNA and protein levels of p50, p52 and p65 were significantly increased after transfection of LV-CircVCAN in OA-chondrocytes. Furthermore, PDTC (NF-κB inhibitor) transfection can significantly reverse the effect of overexpression of CircVCAN on the proliferation and apoptosis of OA chondrocytes.

CONCLUSIONS: CircVCAN is overexpressed in OA tissues and cells. CircVCAN can affect the proliferation and apoptosis of OA chondrocytes by blocking the activation of the NF-κB signaling pathway. Thus, CircVCAN may be an important target molecule for OA treatment.

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