Journal of dental sciences · 2026
Endothelin-1 drives COX-2 and prostaglandin E2 expression in osteoblasts through MAPK/AP-1 signaling during periodontal inflammation.
СтатьяНазвание и аннотация: Перевод в очереди
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Fan Fang-Yu, Vo Thi Thuy Tien, Kuo Hsuan, Tseng Chien-Fu, Lin Wei-Ning, Wu Chia-Yu, Wu Yang-Che, Yang Chuen-Mao, Hsiao Li-Der, Lee I-Ta
Аннотация
BACKGROUND/PURPOSE: Endothelin-1 (ET-1) has been implicated in inflammatory tissue responses, but its role in osteoblast-mediated inflammation during periodontal inflammation remains unclear. This study investigated whether ET-1 induces cyclooxygenase-2 (COX-2) expression and prostaglandin E2 (PGE2) release in osteoblasts and explored the underlying signaling mechanisms.
MATERIALS AND METHODS: Murine osteoblast-like MC3T3-E1 cells were stimulated with ET-1. COX-2 protein and mRNA expression, promoter activity, and PGE2 release were assessed by Western blotting, real-time RT-PCR, luciferase reporter assay, and ELISA, respectively. Pharmacological inhibitors and siRNA knockdown were used to examine the roles of ETA/ETB receptors, Gq/Gi proteins, ERK1/2, p38 MAPK, JNK1/2, and AP-1 signaling.
RESULTS: ET-1 increased COX-2 protein and mRNA expression, COX-2 promoter activity, and PGE2 release in MC3T3-E1 cells in a time-dependent manner. Actinomycin D and cycloheximide significantly reduced ET-1-induced COX-2 expression and PGE2 release, indicating transcriptional and translational regulation. Pharmacological blockade or knockdown of ETA and ETB receptors attenuated these responses. Inhibition or silencing of Gq and Gi also suppressed ET-1-induced COX-2 expression and PGE2 release. Moreover, inhibition or knockdown of ERK1/2, p38 MAPK, or JNK1/2 reduced these effects. ET-1 also promoted c-Jun phosphorylation, nuclear accumulation, AP-1 binding activity, and COX-2 promoter transactivation, whereas AP-1 inhibition or c-Jun knockdown reduced COX-2 expression and downstream PGE2 production.
CONCLUSION: ET-1 drives COX-2 expression and PGE2 release in osteoblasts through ETA/ETB dependent Gi/Gq, MAPK, and AP-1 signaling, supporting a potential role of ET-1 in osteoblast-associated inflammatory responses and inflammatory bone microenvironment changes under periodontal inflammatory conditions.
MATERIALS AND METHODS: Murine osteoblast-like MC3T3-E1 cells were stimulated with ET-1. COX-2 protein and mRNA expression, promoter activity, and PGE2 release were assessed by Western blotting, real-time RT-PCR, luciferase reporter assay, and ELISA, respectively. Pharmacological inhibitors and siRNA knockdown were used to examine the roles of ETA/ETB receptors, Gq/Gi proteins, ERK1/2, p38 MAPK, JNK1/2, and AP-1 signaling.
RESULTS: ET-1 increased COX-2 protein and mRNA expression, COX-2 promoter activity, and PGE2 release in MC3T3-E1 cells in a time-dependent manner. Actinomycin D and cycloheximide significantly reduced ET-1-induced COX-2 expression and PGE2 release, indicating transcriptional and translational regulation. Pharmacological blockade or knockdown of ETA and ETB receptors attenuated these responses. Inhibition or silencing of Gq and Gi also suppressed ET-1-induced COX-2 expression and PGE2 release. Moreover, inhibition or knockdown of ERK1/2, p38 MAPK, or JNK1/2 reduced these effects. ET-1 also promoted c-Jun phosphorylation, nuclear accumulation, AP-1 binding activity, and COX-2 promoter transactivation, whereas AP-1 inhibition or c-Jun knockdown reduced COX-2 expression and downstream PGE2 production.
CONCLUSION: ET-1 drives COX-2 expression and PGE2 release in osteoblasts through ETA/ETB dependent Gi/Gq, MAPK, and AP-1 signaling, supporting a potential role of ET-1 in osteoblast-associated inflammatory responses and inflammatory bone microenvironment changes under periodontal inflammatory conditions.