xinlin yang, phd assistant professor of orthopaedics may 9, 2015
TRANSCRIPT
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Xinlin Yang, PhDAssistant Professor of Orthopaedics
May 9, 2015
Antioxidative Fullerol for Orthopaedic
Diseases
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University of Virginia Orthopaedic Surgery
Fullerene C60 and orthopaedic diseases Fullerene C60 and cell differentiation/function
Research interests
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.
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University of Virginia Orthopaedic Surgery
Fullerene-ROS interactions (Satoh and Takayanagi, 2006)
Fullerene C60
Its antioxidative capacity hundreds times higher than…
Molecular model of Fullerene C60
Drs. Smalley, Curl and Kroto, 1985/1996
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University of Virginia Orthopaedic Surgery
Orthopaedic diseases/OS
(Hendrickx et al., 2015)
Multifactorial diseases Oxidative stress (OS)
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University of Virginia Orthopaedic Surgery
OS/adipo/osteo/pathways
(Atashi et al., 2015)
Oxidative stress Adipogenesis
Oxidative stress Osteogenesis
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University of Virginia Orthopaedic Surgery
Osteoclastogenesis(Kanzaki et al., 2013)
OS/OC/inflammation/pathways
Inflammation(Emre et al., 2007)
Oxidative stress Osteoclastogenesis
Oxidative stress Inflammation
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University of Virginia Orthopaedic Surgery
Biodistribution/Blood clearance
T1/2alpha =1.9 h
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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University of Virginia Orthopaedic Surgery
Osteonecrosis
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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University of Virginia Orthopaedic Surgery
Osteoporosis
RAW264.7 RANKL Fullerol Trap staining qRT-PCR Rabbit MPSL Micro-CT
OC
VB Bone loss
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University of Virginia Orthopaedic Surgery
Disc degeneration
RAW264.7 LPS Fullerol qRT-PCR ELISA Rabbit MPSL Micro-CT
Inflammation
IVDD
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University of Virginia Orthopaedic Surgery
• 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.
Summary
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University of Virginia Orthopaedic Surgery
Future Plans
Novel antioxidative biomaterials
More orthopaedic
diseasesA. B.
C. Fullerene
Fullerene
Drug
Fullerene
BiomaterialScaffold
Our R21 on the topic of fullerene-PLGA for bone repair was scored 22. Release profile is being prepared.
for bone marrow disorders
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University of Virginia Orthopaedic Surgery
• Orthopaedic Research and Education Foundation/Zachary B. Friedenberg Clinician Scientist Award (Dr. Cui)
• NIH/NIAMS R21 AR062732 (Dr. Cui)
Funding Sources