In vitro effects of VA441,a new selective cyclooxygenase-2 inhibitor,on human osteoarthritic chondrocytes exposed to IL-1β

The aim of this in vitro study was to examine the possible effect of [2-methyl-5-(4-methylsulphonyl)phenyl-1-phenyl-3-(2-n-propyloxyethyl)] -1h-pyrrole (va441),a new selective cyclooxygenase (cox)-2 inhibitor,on human osteoarthritic (oa) chondrocyte cultivated in the presence or absence of interleukin-1β (il-1β). in particular,we assessed the effects of 1 and 10 μm of va441,celecoxib,and indomethacin on cell viability,cox-2 and inducible nitric oxide synthase (inos) gene expression,prostaglandin e 2 (pge2) production,and nitric oxide (no) and metalloproteinase-3 (mmp-3) release. furthermore,we carried out morphological assessment by transmission electron microscopy (tem). the presence of il-1β led to a significant increase in pge2,mmp-3,and no production,as well as a significant increase in gene expression of cox-2 and inos. all the drugs tested had a statistically significant inhibitory effect on pge 2 production and gene expression of cox-2 stimulated by il-1β. va441 and celecoxib significantly suppressed il-1β-stimulated mmp-3 and no and inos gene expression in a dose-dependent manner,while indomethacin did not show any significant effect on mmp-3 and no production or on inos gene expression. tem demonstrated that il-1β severely alters the structure of chondrocytes; after coincubation with va441 or celecoxib,the cells recovered their ultrastructure. our data suggest that va441 and celecoxib may have a beneficial effect on chondrocyte metabolism. © the japanese pharmacological society.