OSTEOPROTEGERIN LEVELS INCREASED BY INTERLEUKIN-1β IN HUMAN PERIODONTAL LIGAMENT CELLS ARE SUPPRESSED THROUGH PROSTAGLANDIN E2 SYNTHESIZED DE NOVO

• Published in: Cytokine (Philadelphia, Pa.) Vol. 18; no. 3; pp. 133 - 139
• Main Authors: Sakata, Masatoshi, Shiba, Hideki, Komatsuzawa, Hitoshi, Fujita, Tsuyoshi, Uchida, Yuushi, Yoshino, Hiroshi, Ogawa, Tetsuji, Kawaguchi, Hiroyuki, Kurihara, Hidemi
• Format: Journal Article
• Language: English
• Published: Elsevier Ltd 01.05.2002
• Subjects: IL-1β/OPG/PGE2/periodontal ligament cells; IL-1β/OPG/PGE2/periodontal ligament cells
• ISSN: 1043-4666; 1096-0023
• DOI: 10.1006/cyto.2002.1026

Osteoprotegerin (OPG) is a novel tumor necrosis factor receptor superfamily that inhibits osteoclast differentiation, activity, and survival. Interleukin-1β (IL-1β) increases OPG expression. IL-1β also increases prostaglandin E2 (PGE2) production and stimulates bone resorption. In the present study, we examined the involvement of PGE2 in IL-1β-induced increases in OPG levels in human periodontal ligament cells (HPL cells) in an effort to clarify apparently conflicting IL-1β actions on bone resorption and understand IL-1β-induced increases in secretion of OPG and PGE2 in HPL cells. 5,6-dichloro-1-β-D-ribofuranosyl-benzimidazole, a mRNA synthesis inhibitor, partly inhibited the increase in OPG mRNA levels induced by IL-1β. Cycloheximide, a protein synthesis inhibitor, enhanced the stimulatory effect of IL-1β. Etodolac, a selective cyclooxygenase-2 inhibitor, suppressed the increase in PGE2 levels. Furthermore, etodolac reinforced the promotion of OPG expression by IL-1β at the mRNA and protein levels. PGE2 added to cultures of HPL cells decreased OPG mRNA levels in a dose- and time- dependent manner. These findings suggest that the increase in OPG levels induced by IL-1β in HPL cells is suppressed through PGE2 synthesized de novo.