xinlin yang, phd assistant professor of orthopaedics may 9, 2015
TRANSCRIPT
Xinlin Yang, PhDAssistant Professor of Orthopaedics
May 9, 2015
Antioxidative Fullerol for Orthopaedic
Diseases
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.
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
University of Virginia Orthopaedic Surgery
Orthopaedic diseases/OS
(Hendrickx et al., 2015)
Multifactorial diseases Oxidative stress (OS)
University of Virginia Orthopaedic Surgery
OS/adipo/osteo/pathways
(Atashi et al., 2015)
Oxidative stress Adipogenesis
Oxidative stress Osteogenesis
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
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
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
University of Virginia Orthopaedic Surgery
Osteoporosis
RAW264.7 RANKL Fullerol Trap staining qRT-PCR Rabbit MPSL Micro-CT
OC
VB Bone loss
University of Virginia Orthopaedic Surgery
Disc degeneration
RAW264.7 LPS Fullerol qRT-PCR ELISA Rabbit MPSL Micro-CT
Inflammation
IVDD
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
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
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