The Study on Mechanism of Nf-Κb Signal Molecule In Kashin-Beck Disease

Abstract

Kashin-Beck disease (KBD) is an endemic osteoarthropathy.This study is to observe the change of NF-κB signaling in KBD patients and expression of NF-κB p65 in human C28/I2 chondrocyte for analyzing the effect of NF-κB p65 on chondrocyte apoptosis. 161 Patients with KBD and 312 healthy controls were randomly selected from Shaanxi, China matched by age and sex. Venous blood was collected from patients and healthy controls. The model of C28/I2 chondrocyte oxidative damage was established by using tert-butyl hydroperoxide (tBHP), and cell apoptosis and reactive oxygen species (ROS) was detected by Hoechst 33342 and dichlorofluorescein methods, respectively. The proteins of whole blood and cells was extracted by Trizol method, expression level of NF-κB p65 molecule in whole blood were detected by Western blotting. Compared with age and sex, differences were not statistically significant between KBD group and control group (t=0.336，P=0.737；χ2=0.407，P=0.523). The protein expression level of NF-κB p65 in KBD group was 1.833 times as high as that of control group (P<0.05). In C28/I2 chondrocyte oxidative damage model, the number of cell apoptosis increased in tBHP group and level of ROS and protein expression level of NF-κB p65 were higher than that of control group (P<0.05), however, levels of ROS were lower than that of control group (P<0.05), protein levels of NF-κB p65 were down-regulated in low and middle selenium pre-protection group compared to tBHP group (P>0.05). The NF-κB signaling pathway is up-regulated in KBD patients, moreover, chondrocyte experiments showed cell apoptosis was mediated via up-regulation of NF-κB p65, and the expression of p65 is down-regulated by Na2SeO3intervention, which suggest NF-κB signaling pathway play an important role in pathogenesis of KBD (This research was supported by National Natural Science Foundation in China No.81573104,81172610, 81673117).