Session Type: Abstract Submissions (ACR)
Our previous study has shown that injection of 13-nm gold nanoparticles ameliorates collagen-induced arthritis (CIA) through the inhibition of angiogenesis by binding to VEGF. Fullerene derivatives, strong scavengers of superoxide radicals, have been recently identified as potential therapeutic agents for arthritis, with the ability to inhibit proinflammatory mediators. In this study, we demonstrate amelioration of CIA by treatment with C60(OH)36nanoparticles through the suppression of proinflammatory cytokine production, bone/cartilage erosion and synovial angiogenesis.
Physical properties of newly synthesized C60(OH)36 nanoparticles were characterized by X-ray photoelectron spectrometer, infra-red spectroscopy, fast-atom bombardment and matrix-assisted laser desorption/ionization mass spectroscopy, transmission electron microscope and dynamic light scattering analysis. Their ability to remove superoxide radicals was confirmed by the electron paramagnetic resonance spectrometer and the inhibition of intracellular reactive oxygen species formation in RAW 264.7 cells. Eight-week-old male Sprague-Dawley rats were immunized with bovine type II collagen emulsified in complete Freund’s adjuvant on day 0 and 7. Articular index was used to evaluate the therapeutic effect of the nanoparticles on arthritic joints receiving intra-articular injection of 10 mg nanoparticles or PBS as control (16 joints per group) on day 7. Histological and radiographic scores of arthritic joints were calculated upon sacrifice on day 21. Proinflammatory cytokines (IL-1b and TNF-a) and VEGF concentrations in homogenized synovium extracts were measured by enzyme-linked immunosorbent assay. Synovial angiogenesis was examined by counting microvessel numbers after immunohistochemical staining. The ability of nanoparticles to suppress endothelial cell proliferation was tested by using VEGF-treated human dermal microvascular endothelial cells-1 (HMVEC-1).
Articular indexes of nanoparticles-injected joints were reduced as compared with PBS-treated counterparts. There were lower histological and radiographic scores with less pannus formation and erosion of cartilage/bone in nanoparticles-treated synovium. Reduced IL-1b concentrations were identified in the treatment group. Notably, nanoparticles-treated synovium had decreased microvessel density without reduction of VEGF levels, and nanoparticle treatment inhibited VEGF-induced HMVEC-1 proliferation in a dose-dependent manner, suggesting that the mechanism of angiogenesis inhibition was through the interference in the signal transduction pathway rather than physical adsorption of the growth factor.
This study demonstrates first that intra-articular injection of C60(OH)36 nanoparticles ameliorates CIA through anti-angiogenesis effect, further implicating a novel mechanism in application of certain fullerene derivatives as potential therapeutic agents in rheumatoid joints.
C. T. Weng,
S. Y. Chen,
Y. H. Chen,
C. L. Wu,
M. F. Liu,
A. L. Shiau,
C. R. Wang,
« Back to 2014 ACR/ARHP Annual Meeting
ACR Meeting Abstracts - https://acrabstracts.org/abstract/amelioration-of-collagen-induced-arthritis-by-water-soluble-fullerene-c60oh36-nanoparticles-through-the-inhibition-of-angiogenesis/