Endothelin-1 drives cyclooxygenase-2 and prostaglandin E2 expression in osteoblasts through mitogen-activated protein kinase and activator protein-1 signaling during periodontal inflammation

Authors

• Fang-Yu Fan, School of Dental Technology, College of Oral Medicine, Taipei Medical University, Taipei, Taiwan
• Thi Thuy Tien Vo, Faculty of Dentistry, Nguyen Tat Thanh University, Ho Chi Minh City, Vietnam
• Hsuan Kuo, Division of Oral and Maxillofacial Surgery, Department of Dentistry, Taipei Medical University Hospital, Taipei, Taiwan
• Chien-Fu Tseng, Graduate Institute of Clinical Dentistry, School of Dentistry, College of Medicine, National Taiwan University, Taipei, Taiwan
• Wei-Ning Lin, Graduate Institute of Biomedical and Pharmaceutical Science, Fu Jen Catholic University, New Taipei City, Taiwan
• Chia-Yu Wu, School of Dental Technology, College of Oral Medicine, Taipei Medical University, Taipei, Taiwan
• Yang-Che Wu, School of Dentistry, College of Oral Medicine, Taipei Medical University, Taipei, Taiwan
• Chuen-Mao Yang, Graduate Institute of Biomedical and Pharmaceutical Science, Fu Jen Catholic University, New Taipei City, Taiwan
• Li-Der Hsiao, Graduate Institute of Biomedical and Pharmaceutical Science, Fu Jen Catholic University, New Taipei City, Taiwan
• I-Ta Lee, School of Dentistry, College of Oral Medicine, Taipei Medical University, Taipei, TaiwanFollow

First Page

1411

Last Page

1424

Abstract

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 ET_A/ET_B receptors, G_q/G_i 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 ET_A and ET_B receptors attenuated these responses. Inhibition or silencing of G_q and G_i 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 ET_A/ET_B-dependent G_i/G_q, 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.

Recommended Citation

Fan, Fang-Yu; Tien Vo, Thi Thuy; Kuo, Hsuan; Tseng, Chien-Fu; Lin, Wei-Ning; Wu, Chia-Yu; Wu, Yang-Che; Yang, Chuen-Mao; Hsiao, Li-Der; and Lee, I-Ta (2026) "Endothelin-1 drives cyclooxygenase-2 and prostaglandin E2 expression in osteoblasts through mitogen-activated protein kinase and activator protein-1 signaling during periodontal inflammation," Journal of Dental Sciences: Vol. 21: Iss. 3, Article 9.
Available at: https://jds.ads.org.tw/journal/vol21/iss3/9

Publication Date

2026