TY - JOUR
T1 - Glucosamine and its N-acetyl-phenylalanine derivative prevent TNF-α-induced transcriptional activation in human chondrocytes
AU - D'Abusco, Anna Scotto
AU - Cicione, Claudia
AU - Calamia, Valentina
AU - Negri, Rodolfo
AU - Giordano, Cesare
AU - Grigolo, Brunella
AU - Politi, Laura
AU - Scandurra, Roberto
PY - 2007/11
Y1 - 2007/11
N2 - Objectives: Glucosamine (GlcN) is used in the treatment of osteoarthritis as symptomatic slow-acting drug, but its mode of action is not completely known. We analyzed the influence of GlcN and its N-acetyl-phenylalanine derivative (NAPA) on mRNA transcription level of TNF-α-stimulated genes in cell culture. Methods: Human immortalized chondrocyte cell line lbpva55 was stimulated with TNF-α and treated with GlcN and NAPA. mRNA transcription level of several genes, identified by complementary DNA microarray (cDNA microarray), was validated by Quantitative Real-Time Polymerase Chain Reaction (Q-RT-PCR). Results: Several genes, whose mRNA level was increased by TNF-α treatment and significantly reduced by GlcN and NAPA in lbpva55 cells, were identified. These include cytokine receptors TNF-R1 and TNF-R2, their associated factor TRAF-6, signaling intermediates IGFB-6 and Rnd1, as well as cell cycle regulating proteins CUL-2 and G1S protein 1. Down-regulation of mRNA expression level of some of these genes is in accordance with inactivation of NF-κB transcription factor. Moreover, we found down-regulation of c-jun mRNA level, a component of AP-1 transcription factor. Conclusions: Our study suggests that GlcN and NAPA interfere with activation of NF-κB nd AP-1 transcription factors, which are responsible for the expression of genes involved in diverse biological processes, such as cell growth and death, inflammatory and stress responses, accounting for the beneficial effects of GlcN in osteoarthritis.
AB - Objectives: Glucosamine (GlcN) is used in the treatment of osteoarthritis as symptomatic slow-acting drug, but its mode of action is not completely known. We analyzed the influence of GlcN and its N-acetyl-phenylalanine derivative (NAPA) on mRNA transcription level of TNF-α-stimulated genes in cell culture. Methods: Human immortalized chondrocyte cell line lbpva55 was stimulated with TNF-α and treated with GlcN and NAPA. mRNA transcription level of several genes, identified by complementary DNA microarray (cDNA microarray), was validated by Quantitative Real-Time Polymerase Chain Reaction (Q-RT-PCR). Results: Several genes, whose mRNA level was increased by TNF-α treatment and significantly reduced by GlcN and NAPA in lbpva55 cells, were identified. These include cytokine receptors TNF-R1 and TNF-R2, their associated factor TRAF-6, signaling intermediates IGFB-6 and Rnd1, as well as cell cycle regulating proteins CUL-2 and G1S protein 1. Down-regulation of mRNA expression level of some of these genes is in accordance with inactivation of NF-κB transcription factor. Moreover, we found down-regulation of c-jun mRNA level, a component of AP-1 transcription factor. Conclusions: Our study suggests that GlcN and NAPA interfere with activation of NF-κB nd AP-1 transcription factors, which are responsible for the expression of genes involved in diverse biological processes, such as cell growth and death, inflammatory and stress responses, accounting for the beneficial effects of GlcN in osteoarthritis.
KW - Chondrocyte gene expression
KW - Chondrocytes
KW - Glucosamine
KW - Osteoarthritis
KW - TNF-α stimulation
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M3 - Article
C2 - 18173918
AN - SCOPUS:38149128156
VL - 25
SP - 847
EP - 852
JO - Clinical and Experimental Rheumatology
JF - Clinical and Experimental Rheumatology
SN - 0392-856X
IS - 6
ER -