Antioxidative nanofullerol inhibits macrophage activation and development of osteoarthritis in rats

Abstract

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

Acknowledgments

The work supported by the NIH/National Institute of Arthritis and Musculoskeletal and Skin Diseases grant No. 5R21AR070987 and by Research fund from University of Virginia School of Medicine.

Disclosure

QC reports grants from the NIH the University of Virginia, and Exactech. The authors report no other conflicts of interest in this work.