Transcriptional alteration of matrix-related gene expression in cultured human disc cells by nanoparticles of a bismethanophosphonate fullerene.
Fullerene and its derivatives have been extensively studied in the biomedical field. Their biological activities towards various cell types have been reported, and previous results have implicated their potential uses as photosensitizers in photodynamic therapy of tumour and photoinactivation of bacteria and viruses, antioxidative/cytoprotective reagents and carriers for drug delivery. We describe here the effects of a BMPF (bismethanophosphonate fullerene) on matrix-related gene expression in cultured human disc cells by real-time reverse transcriptase PCR. Mediation of BMPF into water by DMSO leads to formation of an aqueous suspension of nanoparticles (denoted as nano-BMPF) with a very narrow size distribution and an average size of 136.3 nm. Moreover, nano-BMPF could induce a down-regulation of gene expression of matrix proteins aggrecan, type I collagen and type II collagen and an up-regulation of gene expression of matrix metalloproteinase 3. IL-1Ra (IL-1 receptor antagonist), but not IL-1 receptor 1, is transcriptionally inhibited by nano-BMPF. These data indicated a disc degeneration-inducing activity of nano-BMPF, raising concerns of possible adverse effects, while a fullerene-based treatment of disc diseases is employed.
Yang
Xinlin
X
Department of Orthopaedic Surgery, University of Virginia School of Medicine, Charlottesville, VA 22908, U.S.A. xy3c@virginia.edu
Wan
Yueping
Y
Qiao
Xinge
X
Arlet
Vincent
V
Li
Xudong
X
D053674:Aggrecans / Q000235:genetics / Q000378:metabolism; D002478:Cells, Cultured; D024042:Collagen Type I / Q000235:genetics / Q000378:metabolism; D024043:Collagen Type II / Q000235:genetics / Q000378:metabolism; D016326:Extracellular Matrix Proteins / Q000235:genetics / Q000378:metabolism; D037741:Fullerenes / Q000737:chemistry*; D006801:Humans; D007403:Intervertebral Disc / Q000166:cytology / Q000378:metabolism*; D019278:Matrix Metalloproteinase 3 / Q000235:genetics / Q000378:metabolism; D053758:Nanoparticles / Q000737:chemistry*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014158:Transcription, Genetic
D053674:Aggrecans; D024042:Collagen Type I; D024043:Collagen Type II; D016326:Extracellular Matrix Proteins; D037741:Fullerenes; D019278:Matrix Metalloproteinase 3