Nucleus pulposus cell senescence is alleviated by resveratrol through regulating the ROS/NF-κB pathway under high-magnitude compression

Abstract

Mechanical overloading is a risk factor of disc degeneration. Studies have demonstrated that resveratrol helps to maintain the disc cell's healthy biology. The present study aims to investigate whether resveratrol can suppress mechanical overloading-induced nucleus pulposus (NP) cell senescence and the potential mechanism. The isolated rat NP cells were seeded in the decalcified bone matrix (DBM) and cultured under non-compression (control) and compression (20% deformation, 1.0 Hz, 6 h/day) for 5 days using the mechanically active bioreactor. The resveratrol (30 and 60 μM) was added into the culture medium of the compression group to investigate its protective effects against the NP cell senescence. NP cell senescence was evaluated by cell proliferation, cell cycle, senescence-associated β-galactosidase (SA-β-Gal) activity, telomerase (TE) activity, and gene expression of the senescence markers (p16 and p53). Additionally, the reactive oxygen species (ROS) content and activity of the NF-κB pathway were also analyzed. Compared with the non-compression group, the high-magnitude compression significantly promoted NP cell senescence, increased ROS generation and activity of the NF-κB pathway. However, resveratrol partly attenuated NP cell senescence, decreased ROS generation and activity of the NF-κB pathway in a concentration-dependent manner under mechanical compression. Resveratrol can alleviate mechanical overloading-induced NP cell senescence through regulating the ROS/NF-κB pathway. The present study provides that resveratrol may be a potential drug for retarding mechanical overloading-induced NP cell senescence.

Extensive mechanical tension promotes annulus fibrosus cell senescence through suppressing cellular autophagy

“…In light of the decreased matrix anabolism of senescent cells, these results again indirectly suggest that 20% tension promotes AF cell senescence compared with the 5% tension. Though there were no studies about AF cell senescence under mechanical tension previously, lots of previous studies have demonstrated that high magnitude of mechanical stimuli promotes disc NP cell senescence [13–15,29]. Anyway, the present study and other previous studies demonstrate that high magnitude of mechanical stimulation does harm the healthy disc biology and is a risk factor for disc degeneration.…”

Resveratrol attenuates inflammation environment-induced nucleus pulposus cell senescence in vitro

“…Resveratrol has some protective effects in different cell types, such as the anti-inflammatory and anti-aging [19–21]. Moreover, several studies have reported that resveratrol alleviates disc NP cell senescence under stimulation of certain pathological factors [22,23]. In the present study, we mainly aimed to investigate whether resveratrol is able to suppress inflammation environment-mediated NP cell senescence in vitro .…”

Astragaloside IV inhibits astrocyte senescence: implication in Parkinson’s disease

“…Therefore, astrocytes have been displayed to undergo cellular senescence in vitro due to a variety of factors such as replicative lifespan or external stressors. Resveratrol and a p38MAPK inhibitor could reverse the senescent phenotypes, indicating that senescence has been therapeutically targeted [26,27]. In the present study, we have found that small molecule AS-IV inhibits senescent astrocyte phenotypes that include Fig.…”