International Journal of Nanomedicine (Jun 2019)

Antioxidative nanofullerol inhibits macrophage activation and development of osteoarthritis in rats

  • Pei Y,
  • Cui F,
  • Du X,
  • Shang G,
  • Xiao W,
  • Yang X,
  • Cui Q

Journal volume & issue
Vol. Volume 14
pp. 4145 – 4155

Abstract

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Yilun Pei,1,* Fuai Cui,1,2,* Xuejun Du,1 Guowei Shang,1 Wanan Xiao,1 Xinlin Yang,1 Quanjun Cui11Orthopaedic Research Lab, University of Virginia, Charlottesville, VA, USA; 2Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Shandong University, Jinan, Shandong, China*These authors contributed equally to this work Background: There is emerging evidence which suggests that cellular ROS including nitric oxide (NO) are important mediators for inflammation and osteoarthritis (OA). Water-soluble polyhydroxylated fullerene C60 (fullerol) nanoparticle has been demonstrated to have an outstanding ability to scavenge ROS. Purpose: The objective of this study is to assess the effects of fullerol on inflammation and OA by in vitro and in vivo studies.Methods: For in vitro experiments, primary mouse peritoneal macrophages and a macrophage cell line RAW264.7 were stimulated to inflammatory phenotypes by lipopolysaccharide (LPS) in the presence of fullerol. For the animal study, OA model was created by intra-articular injection of monoiodoacetate into the knee joints of rats and fullerol was intravenously injected immediately after OA induction.Results: NO production and pro-inflammatory gene expression induced by LPS was significantly diminished by fullerol in both macrophage cell types. Meanwhile, fullerol could remarkably reduce phosphorylation of p38 mitogen-activated protein kinase, and protein level of transcription factors nuclear factor-kappaB and forkhead box transcription factor 1 within the nucleus. The animal study delineated that systematic administration of fullerol prevented OA, inhibiting inflammation of synovial membranes and the damage toward the cartilage chondrocytes in the OA joints.Conclusion: Antioxidative fullerol may have a potential therapeutic application for OA.Keywords: macrophages, inflammation, osteoarthritis, antioxidant, polyhydroxylated fullerene C60

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