Symptomatic intervertebral disc degeneration appears to be one of the most prevalent causes of chronic low back symptoms. Although therapeutic techniques including surgical removal and tissue engineering have been applied/proposed, the treatment of disc degeneration still remains a great challenge to both clinical physicians and basic scientists. Oxidative stress is regarded to play an important role in the early stages of disc degenerative process. However, therapeutic strategies using antioxidative agents have been ignored in the treatment of disc degeneration, and in particular, there are no reports on the effects of fullerene and its derivatives on disc degeneration published.
The aim of the project is to characterize the inhibitory effects of aqueous solutions of a specific fullerene C60 derivative, bis- methanophosphonate fullerene (BMPF) on degenerative changes of intervertebral disc in vitro and in vivo based on the hypothesis that they might be very effective in the treatment of disc degeneration. Aqueous nanoparticle suspension will be prepared from fullerene and its derivatives including BMPF and C60, a mono- methanophosphonate fullerene, a fullerol and two carboxyfullerenes. Their protective activities against apoptosis and matrix destruction of cultured human disc cells induced by hydrogen peroxide or IL-1 will be investigated. Their inhibitory effects on disc degeneration will be further evaluated by using a rabbit annulus needle puncture model. The present study involving chemical, materials science and biomedicine will provide useful clues to the therapeutic strategy of disc degeneration and possibly lead to some novel potential candidates for the treatment of disc degeneration.

Public Health Relevance

Aqueous nanoparticle suspensions of a fullerene derivative, bis- methanophosphonate fullerene will be prepared by different methods and their protective oxidative scavenging effects will be investigated against apoptotic and matrix destructive changes in the intervertebral disc both in vitro and in vivo.

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Exploratory/Developmental Grants (R21)
Project #
5R21AR057512-02
Application #
8309470
Study Section
Musculoskeletal Tissue Engineering Study Section (MTE)
Program Officer
Wang, Fei
Project Start
2011-08-01
Project End
2014-07-31
Budget Start
2012-08-01
Budget End
2014-07-31
Support Year
2
Fiscal Year
2012
Total Cost
$207,900
Indirect Cost
$72,900
Name
University of Virginia
Department
Orthopedics
Type
Schools of Medicine
DUNS #
065391526
City
Charlottesville
State
VA
Country
United States
Zip Code
22904
Liu, Qihai; Cui, Quanjun; Li, Xudong Joshua et al. (2014) The applications of buckminsterfullerene C60 and derivatives in orthopaedic research. Connect Tissue Res 55:71-9
Yang, Xinlin; Jin, Li; Yao, Lu et al. (2014) Antioxidative nanofullerol prevents intervertebral disk degeneration. Int J Nanomedicine 9:2419-30