title: 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 H2O2 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 H2O2 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 H2O2 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.
authors.affiliation: Orthopaedic Research Laboratories, University of Virginia, Charlottesville, VA, USA.
authors.forename: Xinlin
authors.initials: X
authors.lastname: Yang
authors.affiliation: Orthopaedic Research Laboratories, University of Virginia, Charlottesville, VA, USA.
authors.forename: Li
authors.initials: L
authors.lastname: Jin
authors.affiliation: School of Life Science, Beijing Institute of Technology, Beijing, People's Republic of China ; Research Institute of Beijing Tongrentang Co., Ltd, Beijing, People's Republic of China.
authors.forename: Lu
authors.initials: L
authors.lastname: Yao
authors.affiliation: Orthopaedic Research Laboratories, University of Virginia, Charlottesville, VA, USA.
authors.forename: Francis H
authors.initials: FH
authors.lastname: Shen
authors.affiliation: Orthopaedic Research Laboratories, University of Virginia, Charlottesville, VA, USA.
authors.forename: Adam L
authors.initials: AL
authors.lastname: Shimer
authors.affiliation: Orthopaedic Research Laboratories, University of Virginia, Charlottesville, VA, USA.
authors.forename: Xudong
authors.initials: X
authors.lastname: Li
mesh_terms: D000293:Adolescent; D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage* / Q000737:chemistry; D005260:Female; D037741:Fullerenes / Q000008:administration & dosage* / Q000737:chemistry; D006801:Humans; D066298:In Vitro Techniques; D055959:Intervertebral Disc Degeneration / Q000378:metabolism* / Q000473:pathology / Q000517:prevention & control*; D008297:Male; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry; D009569:Nitric Oxide / Q000378:metabolism*; D011817:Rabbits; D017382:Reactive Oxygen Species / Q000378:metabolism*; D016896:Treatment Outcome
chemical_list: D000975:Antioxidants; D037741:Fullerenes; D017382:Reactive Oxygen Species; C408042:fullerol C60(OH)24; D009569:Nitric Oxide
keywords: antioxidant; extracellular matrix; free radical; fullerol; intervertebral disk