Resveratrol enhances matrix biosynthesis of nucleus pulposus cells through activating autophagy via the PI3K/Akt pathway under oxidative damage

The decrease in nucleus pulposus (NP) matrix production is a classic feature during disc degeneration. Resveratrol (RSV) is reported to play protective effects under many pathological factors.The present study aims to study the effects of RSV on NP matrix homeostasis under oxidative damage and the potential mechanism. Rat NP cells were exposed to H2O2 solution to create an oxidative damage. RSV and the 3-methyladenine (3-MA) were added along with the culture medium to respectively investigate the role of RSV and cellular autophagy. NP matrix synthesis was evaluated by the expression of macromolecules (aggrecan and collagen II) and glycosaminoglycan (GAG) content. Activation of cellular autophagy was assessed by the expression of several molecular markers. Additionally, activity of the PI3K/Akt pathway was also evaluated to study its potential role. Compared with the control group (NP cells treated with H2O2), RSV significantly up-regulated expression of matrix macromolecules (aggrecan and collagen), promoted GAG production, and increased the expression of autophagy-related markers (Beclin-1 and LC-3). Further analysis showed that inhibition of autophagy by 3-MA partly attenuated NP matrix production. Additionally, RSV increased activity of the PI3K/Akt pathway compared with the control NP cells, but it was not affected by the addition of 3-MA. RSV plays a protective role in enhancing NP matrix synthesis under oxidative damage. Mechanistically, activation of the cellular autophagy via the PI3K/Akt pathway may participate in this process. RSV may be an effective drug to attenuate oxidative stress-induced disc degeneration.