Transcript Document

Xinlin Yang, PhD
Assistant Professor of Orthopaedics
May 9, 2015
Research interests
 Fullerene C60 and orthopaedic diseases
 Fullerene C60 and cell differentiation/function
Yang X, Li CJ, Wan Y, Smith P, Shang G, Cui Q. Antioxidative fullerol promotes osteogenesis of
human adipose-derived stem cells. Int J Nanomedicine. 2014 Aug 20;9:4023-31.
Yang X, Jin L, Yao L, Shen FH, Shimer AL, Li X. Antioxidative nanofullerol prevents intervertebral disk
degeneration. Int J Nanomedicine. 2014 May 15;9:2419-30.
Yang X, Ebrahimi A, Li J, Cui Q. Fullerene-biomolecule conjugates and their biomedicinal
applications. Int J Nanomedicine. 2014;9:77-92. Review.
Liu H, Yang X, Zhang Y, Dighe A, Li X, Cui Q. Fullerol antagonizes dexamethasone-induced oxidative
stress and adipogenesis while enhancing osteogenesis in a cloned bone marrow mesenchymal stem
cell. J Orthop Res. 2012 Jul;30(7):1051-7.
Yang X, Wan Y, Qiao X, Arlet V, Li X. Transcriptional alteration of matrix-related gene expression in
cultured human disc cells by nanoparticles of a bismethanophosphonate fullerene. Cell Biol Int.
2010 Aug;34(8):837-44.
University of Virginia
Orthopaedic Surgery
Fullerene C60
 Drs. Smalley, Curl and
Kroto, 1985/1996
Fullerene-ROS interactions
(Satoh and Takayanagi, 2006)
Molecular model of
Fullerene C60
 Its antioxidative
capacity hundreds
times higher than…
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Orthopaedic Surgery
Orthopaedic diseases/OS
 Multifactorial diseases
 Oxidative stress (OS)
(Hendrickx et al., 2015)
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OS/adipo/osteo/pathways
 Oxidative stress
Adipogenesis
 Oxidative stress
Osteogenesis
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(Atashi et al., 2015)
OS/OC/inflammation/pathways
Osteoclastogenesis
Inflammation
(Kanzaki et al., 2013)
(Emre et al., 2007)
 Oxidative stress
Osteoclastogenesis
 Oxidative stress
Inflammation
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Biodistribution/Blood clearance
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T1/2alpha =1.9 h
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rabbit
TC99m-Fullerol
SPECT/
γ counter
 Retained in bone
marrow for up to 48 h
 Half time of 1.9 h in
blood
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Osteonecrosis
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D1 & hBMSC
Fullerol
ARS staining
ORO staning
qRT-PCR
Rabbit
MPSL
H & E staining
 ROS
 Osteo
 Adipo
 Pending
histological
data of FH
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Osteoporosis
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RAW264.7
RANKL
Fullerol
Trap staining
qRT-PCR
Rabbit
MPSL
Micro-CT
 OC
 VB Bone
loss
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Orthopaedic Surgery
Disc degeneration
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RAW264.7
LPS
Fullerol
qRT-PCR
ELISA
Rabbit
MPSL
Micro-CT
 Inflammation
 IVDD
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Orthopaedic Surgery
Summary
• Fullerol is enriched in the femoral bone
marrow.
• Fullerol regulates differentiation of bone
marrow stem cells and monocytic
progenitors.
• Fullerene as a powerful antioxidant could
potentially be used for treatment of
osteonecrosis, osteoporosis and
intervertebral disc degeneration.
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Future Plans
Drug
Fullerene
A.
More
orthopaedic
diseases
Fullerene
B.
for bone marrow
disorders
 Our R21 on the topic of
Fullerene
fullerene-PLGA for bone
repair was scored 22.
Release profile is being
prepared.
Novel antioxidative biomaterials
C.
Biomaterial
Scaffold
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Orthopaedic Surgery
Funding Sources
• Orthopaedic Research and Education
Foundation/Zachary B. Friedenberg Clinician
Scientist Award (Dr. Cui)
• NIH/NIAMS R21 AR062732 (Dr. Cui)
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Orthopaedic Surgery