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 #
1R21AR057512-01A2
Application #
8048721
Study Section
Musculoskeletal Tissue Engineering Study Section (MTE)
Program Officer
Wang, Fei
Project Start
2011-08-01
Project End
2013-07-31
Budget Start
2011-08-01
Budget End
2012-07-31
Support Year
1
Fiscal Year
2011
Total Cost
$173,250
Indirect Cost
Name
University of Virginia
Department
Orthopedics
Type
Schools of Medicine
DUNS #
065391526
City
Charlottesville
State
VA
Country
United States
Zip Code
22904
Yeh, Ching-Hua; Chen, Dennis; Aghdasi, Bayan et al. (2018) Link protein N-terminal peptide and fullerol promote matrix production and decrease degradation enzymes in rabbit annulus cells. Connect Tissue Res 59:191-200
Jin, Li; Balian, Gary; Li, Xudong Joshua (2018) Animal models for disc degeneration-an update. Histol Histopathol 33:543-554
Xiao, Li; Hong, Kwangseok; Roberson, Charles et al. (2018) Hydroxylated Fullerene: A Stellar Nanomedicine to Treat Lumbar Radiculopathy via Antagonizing TNF-?-Induced Ion Channel Activation, Calcium Signaling, and Neuropeptide Production. ACS Biomater Sci Eng 4:266-277
Ding, Mengmeng; Jin, Li; Xie, Lin et al. (2018) A Murine Model for Human ECO Syndrome Reveals a Critical Role of Intestinal Cell Kinase in Skeletal Development. Calcif Tissue Int 102:348-357
Xiao, L; Ding, M; Fernandez, A et al. (2017) Curcumin alleviates lumbar radiculopathy by reducing neuroinflammation, oxidative stress and nociceptive factors. Eur Cell Mater 33:279-293
Xiao, Li; Ding, Mengmeng; Saadoon, Osama et al. (2017) A novel culture platform for fast proliferation of human annulus fibrosus cells. Cell Tissue Res 367:339-350
Xiao, Li; Ding, Mengmeng; Zhang, Yi et al. (2017) A Novel Modality for Functional Imaging in Acute Intervertebral Disk Herniation via Tracking Leukocyte Infiltration. Mol Imaging Biol 19:703-713
Yeh, Ching-Hua; Jin, Li; Shen, Francis et al. (2016) miR-221 attenuates the osteogenic differentiation of human annulus fibrosus cells. Spine J 16:896-904
Yang, Xinlin; Jin, Li; Yao, Lu et al. (2014) Antioxidative nanofullerol prevents intervertebral disk degeneration. Int J Nanomedicine 9:2419-30
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

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