title: Chondroprotective effect of three different classes of anti-inflammatory agents on human osteoarthritic chondrocytes exposed to IL-1β.
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.
authors: Department of Medicine, Surgery and Neuroscience, Rheumatology Unit, University of Siena, Policlinico Le Scotte, Viale Bracci 1, 53100 Siena, Italy. Electronic address: saracheleschi@hotmail.com.
authors: Sara
authors: S
authors: Cheleschi
authors: Department of Medicine, Surgery and Neuroscience, Rheumatology Unit, University of Siena, Policlinico Le Scotte, Viale Bracci 1, 53100 Siena, Italy.
authors: Nicola Antonio
authors: NA
authors: Pascarelli
authors: Department of Life Sciences and Biotechnology, University of Ferrara, Via Borsari 46, 44100 Ferrara, Italy; Dept. of Food and Nutrition, Kyung Hee University, Seoul, Republic of Korea.
authors: Giuseppe
authors: G
authors: Valacchi
authors: Department of Biotechnology, Chemistry and Pharmacy, University of Siena, Via Aldo Moro I, 53100 Siena, Italy.
authors: Angela
authors: A
authors: Di Capua
authors: Department of Chemistry and Pharmaceutical Technology, University "La Sapienza", P.le A. Moro 5, I-00185 Rome, Italy.
authors: Mariangela
authors: M
authors: Biava
authors: Department of Life Sciences and Biotechnology, University of Ferrara, Via Borsari 46, 44100 Ferrara, Italy.
authors: Giuseppe
authors: G
authors: Belmonte
authors: Rottapharm-Biotech, Via Valosa di Sopra 7/9, I-20052 Monza, Italy.
authors: Antonio
authors: A
authors: Giordani
authors: Department of Life Sciences and Biotechnology, University of Ferrara, Via Borsari 46, 44100 Ferrara, Italy.
authors: Claudia
authors: C
authors: Sticozzi
authors: Department of Biotechnology, Chemistry and Pharmacy, University of Siena, Via Aldo Moro I, 53100 Siena, Italy.
authors: Maurizio
authors: M
authors: Anzini
authors: Department of Medicine, Surgery and Neuroscience, Rheumatology Unit, University of Siena, Policlinico Le Scotte, Viale Bracci 1, 53100 Siena, Italy.
authors: Antonella
authors: A
authors: Fioravanti
mesh_terms: D000368:Aged; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D018929:Cell Culture Techniques; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D019902:Chondrocytes / Q000187:drug effects* / Q000276:immunology; D051546:Cyclooxygenase 2 / Q000235:genetics; D015232:Dinoprostone / Q000032:analysis / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D053583:Interleukin-1beta / Q000494:pharmacology*; D020782:Matrix Metalloproteinases / Q000235:genetics; D008875:Middle Aged; D015394:Molecular Structure; D016328:NF-kappa B / Q000276:immunology; D009288:Naproxen / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D009566:Nitrates / Q000737:chemistry / Q000494:pharmacology*; D015207:Osteoarthritis, Hip / Q000276:immunology*; D011758:Pyrroles / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D053583:Interleukin-1beta; D016328:NF-kappa B; D009566:Nitrates; D011758:Pyrroles; C000608356:VA 694; C111751:naproxen-n-butyl nitrate; D009288:Naproxen; D051546:Cyclooxygenase 2; D020782:Matrix Metalloproteinases; D015232:Dinoprostone
keywords: Chondrocyte; Cyclooxigenase inhibitor nitric oxide donors; Naproxen; Nitric oxide-selective cyclooxigenase-2 inhibitors; Osteoarthritis; VA694