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

Abstract: 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. [Copyright &y& Elsevier]