Please use this identifier to cite or link to this item: http://hdl.handle.net/20.500.12779/6568
Title: Chondroprotective effect of three different classes of anti-inflammatory agents on human osteoarthritic chondrocytes exposed to IL-1β. S. Cheleschi, N. A. Pascarelli, G. Valacchi, A. Di Capua, M. Biava, G. belmonte, A. Giordani, C. Sticozzi, M. Anzini, A. Fioravanti
Authors: CHELESCHI, SARA
PASCARELLI, NICOLA ANTONIO
Valacchi, Giuseppe
DI CAPUA, ANGELA
Biava, Mariangela
Belmonte, Giuseppe
Giordani, Antonio
Sticozzi, Claudia
Anzini, Maurizio 
Fioravanti, Antonella
Keywords: Chondrocyte; Cyclooxigenase inhibitor nitric oxide donors; Naproxen; Nitric oxide-selective cyclooxigenase-2 inhibitors; Osteoarthritis; VA694
Issue Date: 2015
Project: None 
Journal: INTERNATIONAL IMMUNOPHARMACOLOGY
Abstract: 
VA694, a promising cyclooxigenase-2 (COX-2)-inhibiting hybrid drug endowed with nitric oxide (NO) releasing properties (NO-COXIB), showed COX-2-selective inhibitory effects, associated with interesting anti-inflammatory and anti-nociceptive activities. Therefore, we studied the effects of VA694 on cartilage metabolism, in comparison with Naproxcinod, a COX inhibitor and NO donor (CINOD), and Naproxen, a traditional non-steroidal-anti-inflammatory drug (NSAID) on human osteoarthritic chondrocyte cultures. IL-1β-stimulated chondrocytes showed a significant decrease in cell viability (P<0.001). VA694, Naproxcinod and Naproxen alone didn't significantly affect cell viability, while it restored cell viability in cultures stimulated by IL-1β. The presence of IL-1β determined a significant increase (P<0.001) in PGE2 levels measured by an ELISA assay, and in COX-2 and MMP-3, -9, and -13 gene expression analyzed by RT-PCR. VA694, Naproxcinod and Naproxen, at both concentrations analyzed, significantly counteracted the negative effects induced by IL-1β. VA694, Naproxcinod and Naproxen pre-treatment were able to inhibit IL-1β-induced NF-κB activation, when measured as its nuclear translocation (p50 and p65 subunits). Naproxcinod and Naproxen pre-treatment didn't affect cytoplasmic NF-κB levels; VA694 decreased the cytoplasmic levels of both subunits. Our data suggest that VA694, Naproxcinod and Naproxen, exert anti-inflammatory and chondroprotective effects on OA chondrocytes.
Description: 
204533
URI: http://hdl.handle.net/20.500.12779/6568
ISSN: 1567-5769
DOI: 10.1016/j.intimp.2015.07.003
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