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Published on: March 29, 2018
Prostaglandin E2 EP4 agonist (ONO-4819) accelerates BMP-induced osteoblastic differentiation
Keisuke Nakagawa1, Yuuki Imai, Yoichi Ohta
1Department of Orthopaedic Surgery, Osaka City University Graduate School of Medicine, Asahimachi 1-4-3, Osaka 545-8585, Japan. k-nakagawa@msic.med.osaka-cu.ac.jp
Bone
|August 8, 2007
Summary
Prostaglandin EP4 receptor agonist (EP4A) enhances bone morphogenetic proteins (BMPs) efficacy in promoting bone formation. This study reveals EP4A accelerates BMP-induced osteoblastic differentiation via the PKA signaling pathway.
Area of Science:
- Biochemistry
- Molecular Biology
- Orthopedics
Background:
- Bone morphogenetic proteins (BMPs) induce cartilage and bone formation.
- Agents enhancing BMPs can improve bone repair and shorten treatment times.
- Prostaglandin E2 EP4 receptor selective agonists (EP4A) were investigated for their potential to modulate BMP efficacy.
Purpose of the Study:
- To investigate the mechanisms by which EP4A accelerates BMP-mediated bone formation.
- To examine the effect of EP4A on BMP signaling in vitro.
- To elucidate the intracellular signaling pathways involved in EP4A's bone anabolic effects.
Main Methods:
- Utilized an in vitro system with the pluripotent stromal cell line, ST2.
- Measured mRNA expression of Osterix and Alkaline Phosphatase (ALP).
- Assessed ALP enzymatic activity and the effect of PKA inhibitor pre-treatment.
Main Results:
- BMP treatment significantly elevated Osterix and ALP mRNA expression and ALP activity in ST2 cells.
- Addition of EP4A further enhanced these BMP-induced effects.
- Pre-treatment with a PKA inhibitor abolished the accelerated BMP action by EP4A.
Conclusions:
- ONO-4819 (EP4A) accelerates BMP-induced osteoblastic differentiation in ST2 cells.
- EP4A stimulates commitment to the osteoblastic lineage.
- The Protein Kinase A (PKA) signaling pathway is likely the primary intracellular mediator for EP4's anabolic effects on bone and mineral metabolism.
