Antioxidative nanofullerol prevents intervertebral disk degeneration

Abstract

Compelling evidence suggests that reactive oxygen species (ROS) play a pivotal role in disk degeneration. Fullerol nanoparticles prepared in aqueous solution have been demonstrated to have outstanding ability to scavenge ROS. In this report, in vitro and in vivo models were used to study the efficacy of fullerol in preventing disk degeneration. For in vitro experiments, a pro-oxidant H 2 O 2 or an inflammatory cytokine interleukin (IL)-1β was employed to induce degenerated phenotypes in human nucleus pulposus cells encapsulated in alginate beads, and fullerol was added in the culture medium. For the animal study, an annulus-puncture model with rabbit was created, and fullerol was injected into disks. It was shown that cytotoxicity and cellular ROS level induced by H 2 O 2 were significantly diminished by fullerol. IL-1β-induced nitric oxide generation in culture medium was suppressed by fullerol as well. Gene-profile and biochemical assays showed that fullerol effectively reversed the matrix degradation caused by either H 2 O 2 or IL-1β. The animal study delineated that intradiskal injection of fullerol prevented disk degeneration, increasing water and proteoglycan content and inhibiting ectopic bone formation. These results suggest that antioxidative fullerol may have a potential therapeutic application for disk degeneration.

Anti-inflammatory Chitosan/Poly-γ-glutamic acid nanoparticles control inflammation while remodeling extracellular matrix in degenerated intervertebral disc

“…Moreover, NPs can be easily combined with hydrogels for cell delivery or nucleus pulposus regeneration, increasing the functionality of biomaterials for IVD [47,48]. Examples of NPs are fullerol NPs (approximately 25-50 nm size) that decreased IVD degeneration in human cells and rabbits [49]. NPs are low viscous vehicle, thus easy to inject into the IVD.…”

ROS: Crucial Intermediators in the Pathogenesis of Intervertebral Disc Degeneration

“…In this microenvironment, various exogenous stimuli, such as mechanical loading, high oxygen tension, high glucose stress, and proinflammatory cytokines, increase ROS production in disc cells (Figure 2). Furthermore, ROS themselves also enhance ROS production in disc cells, forming a positive feedback loop [14, 15, 20–24, 36, 44, 56–60]. …”

“…Numerous studies have shown that H 2 O 2 significantly downregulated the expression of collagen type II and aggrecan in human and rat disc cells [14, 15, 36, 38, 41, 44]. ROS overproduction induced by proinflammatory cytokines or high oxygen tension prominently suppressed the matrix synthesis and upregulated the expression of matrix degradation proteases in human and rat disc cells [14, 15, 21, 36, 44, 57]. ROS also caused a dramatic loss of PGs, collagens, and fibronectin in mouse discs [78].…”

Molecular Mechanisms of Intervertebral Disc Degeneration

“…140 Several studies have shown hydrogen peroxide to down regulate the expression of collagen type II and aggrecan in both human and rat disc cells. 126,[141][142][143][144][145] In addition, pro-inflammatory cytokines leading to ROS overproduction have been shown to suppress matrix synthesis and increase the expression of matrix degradation proteases in human and rat disc cells. 126,137,[141][142][145][146] ROS is also known to form positive feedback loops that enhance ROS production in disc cells.…”

“…126,[141][142][143][144][145] In addition, pro-inflammatory cytokines leading to ROS overproduction have been shown to suppress matrix synthesis and increase the expression of matrix degradation proteases in human and rat disc cells. 126,137,[141][142][145][146] ROS is also known to form positive feedback loops that enhance ROS production in disc cells. 126,136,141,[145][146][147][148][149][150] Figure 3.…”