xinlin yang, phd assistant professor of orthopaedics may 9, 2015

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