The effect of nitric oxide on the production of prostaglandin E2 by hydroxyapatite-stimulated a human osteoblast (HOS) cell line

The aim of the present study was to determine the effect of nitric oxide (NO) on the production of prostaglandin E-2 (PGE(2)) by a human osteoblast cell line (HOS cells) stimulated with hydroxyapatite. Cells were cultured on the HA surfaces with or without the presence of NO donors (SNAP and NAP) for 3 days. The effect of NO scavenger, carboxy PTIO, or endothelial nitric oxide synthase (eNOS) inhibitor, L-NIO, was assessed by adding this scavenger in the cultures of HA-stimulated HOS cells with or without the presence of SNAP. Furthermore, HOS cells were pre-treated with anti-human integrin alpha V antibody, indomethacin, a non-specific inhibitor, aspirin, a COX-1 inhibitor, or nimesulide, a COX-2 inhibitor, prior to culturing on HA surfaces with or without the presence of SNAP. The levels of PGE(2) were determined from the 3 day culture supernatants. The results showed that the production of PGE(2) by HA-stimulated HOS cells was augmented by SNAP. Carboxy PTIO suppressed but L-NIO only partially inhibited the production of PGE(2) by HA-stimulated HOS cells with or without the presence of exogenous NO. Pre-treatment of the cells with anti-human integrin alpha V antibody, indomethacin or nimesulide but not aspirin suppressed the production of PGE2 by HA-stimulated HOS cells with or without the presence of NO. Therefore, the results of the present study suggest that NO may up-regulate the production of PGE(2) by augmenting the COX-2 pathway initiated by the binding between HOS cell-derived. integrin aV and HA surface. (c) 2006 Elsevier SAS. All rights reserved.