التفاصيل البيبلوغرافية
| العنوان: |
FXR Activation Accelerates Early Phase of Osteoblast Differentiation Through COX-2-PGE2-EP4 Axis in BMP-2-Induced Mouse Mesenchymal Stem Cells |
| المؤلفون: |
Ko Fujimori, Yusuke Iguchi, Yukiko Yamashita, Keigo Gohda, Naoki Teno |
| المصدر: |
Molecules, Vol 30, Iss 1, p 58 (2024) |
| بيانات النشر: |
MDPI AG, 2024. |
| سنة النشر: |
2024 |
| المجموعة: |
LCC:Organic chemistry |
| مصطلحات موضوعية: |
mesenchymal stem cells, osteoblasts, FXR, COX-2, PGE2, Organic chemistry, QD241-441 |
| الوصف: |
Farnesoid X receptor (FXR), a nuclear receptor, is expressed in calvaria and bone marrow stromal cells and plays a role in bone homeostasis. However, the mechanism of FXR-activated osteoblast differentiation remains unclear. In this study, we investigated the regulatory mechanism underlying FXR-activated osteoblast differentiation using bone morphogenetic protein-2 (BMP-2)-induced mouse ST-2 mesenchymal stem cells. We also synthesized a novel FXR agonist, FLG390, and compared its biological effects in osteoblast differentiation with a known FXR agonist, chenodeoxycholic acid (CDCA). As an FXR agonist, FLG390 accelerated osteoblast differentiation to a comparable extent with CDCA, enhancing alkaline phosphatase (ALP) activity and the expression of osteoblast differentiated-related genes such as ALP, collagen type 1 α1 chain (COL1A1), and runt-related transcription factor 2 (RUNX2). FXR activation elevated the expression of cyclooxygenase (COX)-2 and the production of prostaglandin (PG) E2 in the early phase of osteoblast differentiation. A selective COX-2 inhibitor and an antagonist of EP4 receptors, one of PGE2 receptors, partially suppressed FXR-activated osteoblast differentiation. Moreover, treatment with either inhibitor during the first 6 h after initiating osteoblast differentiation repressed FXR-activated osteoblast differentiation to the same extent as did the treatment for 6 d. Therefore, a novel FXR agonist, FLG390, exhibited potency comparable to CDCA. FXR activation promoted the early phase of osteoblast differentiation via the COX-2-PGE2-EP4 axis, representing a potential target for control of bone metabolism. |
| نوع الوثيقة: |
article |
| وصف الملف: |
electronic resource |
| اللغة: |
English |
| تدمد: |
1420-3049 |
| Relation: |
https://www.mdpi.com/1420-3049/30/1/58; https://doaj.org/toc/1420-3049 |
| DOI: |
10.3390/molecules30010058 |
| URL الوصول: |
https://doaj.org/article/4a40028014174cd184302d2ba5edb577 |
| رقم الانضمام: |
edsdoj.4a40028014174cd184302d2ba5edb577 |
| قاعدة البيانات: |
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