Amelioration of collagen-induced arthritis in rats by nanogold.
OBJECTIVE
Angiogenesis plays a part in the pathogenesis of rheumatoid arthritis (RA), and nanogold inhibits the activity of an angiogenic factor, vascular endothelial growth factor (VEGF). We therefore investigated whether intraarticular delivery of nanogold ameliorates collagen-induced arthritis (CIA) in rats.


METHODS
Binding of 13-nm nanogold to VEGF in human RA synovial fluid (SF) and its effects on RA SF-induced endothelial cell proliferation and migration were assessed. Nanogold was administered intraarticularly to rats with CIA before the onset of arthritis. Progression of CIA was monitored by measures of clinical, radiologic, and histologic changes. In addition, the microvessel density and extent of infiltrating macrophages as well as levels of tumor necrosis factor alpha (TNFalpha) and interleukin-1beta (IL-1beta) in the ankle joints were determined.


RESULTS
Nanogold bound to VEGF in RA SF, resulting in inhibition of RA SF-induced endothelial cell proliferation and migration. Significant reductions in ankle circumference, articular index scores, and radiographic scores were observed in the nanogold-treated rats with CIA compared with their control counterparts. In addition, the histologic score (of synovial hyperplasia, cartilage erosion, and leukocyte infiltration), microvessel density, macrophage infiltration, and levels of TNFalpha and IL-1beta were also significantly reduced in the ankle joints of nanogold-treated rats.


CONCLUSIONS
Our results are the first to demonstrate that intraarticular administration of nanogold ameliorates the clinical course of CIA in rats. Nanogold exerted antiangiogenic activities and subsequently reduced macrophage infiltration and inflammation, which resulted in attenuation of arthritis. These results demonstrate proof of principle for the use of nanogold as a novel therapeutic agent for the treatment of RA.
Tsai
Chiau-Yuang
CY
National Cheng Kung University, Tainan, Taiwan.
Shiau
Ai-Li
AL
Chen
Shih-Yao
SY
Chen
Yu-Hung
YH
Cheng
Pai-Chiao
PC
Chang
Meng-Ya
MY
Chen
Dong-Hwang
DH
Chou
Chen-Hsi
CH
Wang
Chrong-Reen
CR
Wu
Chao-Liang
CL
D000818:Animals; D001172:Arthritis, Rheumatoid / Q000139:chemically induced / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000473:pathology; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D003094:Collagen; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D042783:Endothelial Cells / Q000187:drug effects; D006046:Gold / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D007249:Inflammation / Q000188:drug therapy; D007270:Injections, Intra-Articular; D008264:Macrophages / Q000187:drug effects; D008297:Male; D053768:Metal Nanoparticles / Q000008:administration & dosage / Q000627:therapeutic use*; D009389:Neovascularization, Pathologic / Q000188:drug therapy* / Q000473:pathology; D011859:Radiography; D051381:Rats; D017207:Rats, Sprague-Dawley; D013583:Synovial Membrane / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D042461:Vascular Endothelial Growth Factor A / Q000187:drug effects
D016207:Cytokines; D042461:Vascular Endothelial Growth Factor A; D006046:Gold; D003094:Collagen