title: Fullerol nanoparticles suppress inflammatory response and adipogenesis of vertebral bone marrow stromal cells--a potential novel treatment for intervertebral disc degeneration.
abstract: BACKGROUND
  Intervertebral disc degeneration, leading to chronic back pain, is a major health problem in western societies. Vertebral bone marrow has been considered to play an important role in nutrition supply and metabolic exchange for discs. Vertebral bone marrow lesions, including fatty marrow replacement and inflammatory edema, noted on magnetic resonance imaging were first described in 1988.
  
  
  OBJECTIVE
  To investigate the potential of a free radical scavenger, fullerol nanoparticles, to prevent vertebral bone marrow lesion and prevent disc degeneration by inhibiting inflammation and adipogenic differentiation of vertebral bone marrow stromal cells (vBMSCs).
  
  
  METHODS
  Fullerol nanoparticle solutions were prepared to test their in vitro suppression effects on mouse vBMSC inflammation and adipogenic differentiation compared with non-fullerol-treated groups.
  
  
  METHODS
  With or without fullerol treatment, vBMSCs from Swiss Webster mice were incubated with 10 ng/mL interleukin-1 β (IL-1 β). The intracellular reactive oxygen species (ROS) were measured with fluorescence staining and flow cytometry. In addition, vBMSCs were cultured with adipogenic medium (AM) with or without fullerol. Gene and protein expressions were evaluated by real-time polymerase chain reaction and histologic methods.
  
  
  RESULTS
  Fluorescence staining and flow cytometry results showed that IL-1 β markedly increased intracellular ROS level, which could be prevented by fullerol administration. Fullerol also decreased the basal ROS level to 77%. Cellular production of matrix metalloproteinase (MMP)-1, 3, and 13 and tumor necrosis factor alpha (TNF-α) induced by IL-1 β was suppressed by fullerol treatment. Furthermore, adipogenic differentiation of the vBMSCs was retarded markedly by fullerol as revealed by less lipid droplets in the fullerol treatment group compared with the adipogenic group. The expression of adipogenic genes PPARγ and aP2 was highly elevated with AM but decreased on fullerol administration.
  
  
  CONCLUSIONS
  These results suggest that fullerol prevents the catabolic activity of vBMSCs under inflammatory stimulus by decreasing the level of ROS, MMPs, and TNF-α. Also, fat formation in vBMSCs is prevented by fullerol nanoparticles, and, therefore, fullerol may warrant further in vivo investigation as an effective biological therapy for disc degeneration.
authors.affiliation: Department of Orthopedic Surgery, University of Virginia, Hospital Drive, Cobb Hall B039, P.O. Box 800374, Charlottesville, VA 22908, USA.
authors.forename: Qihai
authors.initials: Q
authors.lastname: Liu
authors.forename: Li
authors.initials: L
authors.lastname: Jin
authors.forename: Francis H
authors.initials: FH
authors.lastname: Shen
authors.forename: Gary
authors.initials: G
authors.lastname: Balian
authors.forename: Xudong Joshua
authors.initials: XJ
authors.lastname: Li
mesh_terms: D050156:Adipogenesis / Q000187:drug effects*; D000818:Animals; D037741:Fullerenes / Q000494:pharmacology* / Q000627:therapeutic use; D007249:Inflammation / Q000188:drug therapy* / Q000378:metabolism; D053583:Interleukin-1beta / Q000494:pharmacology; D055959:Intervertebral Disc Degeneration / Q000188:drug therapy*; D020782:Matrix Metalloproteinases / Q000378:metabolism; D059630:Mesenchymal Stem Cells / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D053758:Nanoparticles; D017382:Reactive Oxygen Species / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D037741:Fullerenes; D053583:Interleukin-1beta; D017382:Reactive Oxygen Species; D014409:Tumor Necrosis Factor-alpha; D020782:Matrix Metalloproteinases
keywords: Adipogenesis; Fullerol; Inflammation; Reactive oxygen species; Vertebral bone marrow