Differential effect of chondroitin-4-sulfate on the immediate and delayed prostaglandin E2 release from osteoblasts

The present study examines the effect of chondroitin-4-sulfate (C4S) on the immediate (non-inflammatory conditions) and the delayed (inflammatory conditions) prostaglandin E₂ (PGE₂) release from rat calvarial osteoblasts. An immediate low release of PGE₂ was induced by PAF, phorbol ester and arachidonic acid but not by IL1β, TNF-α and LPS whereas a delayed high release of PGE₂ was induced by the inflammatory agents IL1β, TNF-α and LPS but not by PAF, phorbol ester and arachidonic acid. C4S had no effect on the immediate PGE₂ release but inhibited the delayed release of PGE₂. IL1β, TNF-α and LPS enhanced the expression of COX-2 and mPGES1 whereas phorbol ester enhanced COX-2 expression only. PAF and arachidonic acid had no effect on the expression of COX-2 and mPGES1. C4S inhibited the enhanced expression of COX-2 and mPGES1 but had no effect on the IL1β-induced decrease of I-κBα and nuclear translocation of NF-κB. These results indicate that the beneficial effects of C4S in bone inflammatory diseases might be due to a specific inhibition of the delayed high PGE₂ release from osteoblasts.