NF-κB inhibitor QNZ protects human chondrocyte degeneration by promoting glucose uptake through Glut4 activation.

Abstract

Glucose is not only an energy source but also raw material for proteoglycan biosynthesis of chondrocyte. The aim of the present study is to explore the role of QNZ in the progress of chondrocytes glucose uptake and investigate whether it will improve the chondrocytes degeneration through Glut4 activation. We isolated human chondrocytes from the cartilage by the patients who underwent total knee arthroplasty operations. Chondrocytes were pretreated with insulin or QNZ for 24 h. The uptake of glucose with stimulation, as well as the expression of Glut4, collagen II, aggrecan, MMP13, TNF-α, PCNA, and the p16 levels were determined by Western blot, quantitative reverse-transcription polymerase chain reaction (qPCR), or immunofluorescence. Both insulin and QNZ stimuli to chondrocytes contributed to the expression of Glut4 and glucose uptake compared to the normal cells. Additionally, collagen II and aggrecan expression was detected to a significant increase, along with the reduced levels of MMP13 and TNF-α after exposed to QNZ. Moreover, QNZ protected chondrocytes degeneration via promoting proliferation and delaying aging. After blocking Glut4, the glucose uptake significantly reduced in QNZ treatment, as well as the expression of collagen II and aggrecan. However, no significant changes were noticed in the MMP13 and TNF-α levels. The present study demonstrates that inhibition of NF-κB activation by QNZ would improve the glucose uptake through Glut4 activation, which plays an important role in the protection of chondrocytes degeneration.