Journal article
Prostaglandin E2 Modulates Bone Morphogenetic Protein-2 Induced Osteogenic Differentiation on a Biomimetic 3D Nanofibrous Scaffold
Journal of biomedical nanotechnology, Vol.14(4), pp.747-755
04/01/2018
DOI: 10.1166/jbn.2018.2490
PMID: 31352948
Abstract
It is a significant challenge to improve the efficacy of biomaterials-delivered bone morphogenetic proteins (i.e., BMP2 and 7) for bone repair. Emerging evidences suggest the traditionally inflammatory factor, prostaglandin E2 (PGE2), may serve as an intriguing target to promote bone regeneration through modulating both inflammation and osteogenesis. Therefore, we developed a three-dimensional (3D) bone matrix-mimicking nanofibrous gelatin scaffold to study the role of PGE2 and a novel and highly selective EP4 receptor agonist (EP4A), CAY10598, in osteogenic differentiation in vitro and bone formation in a mouse model. Our data indicated that EP4A, similar to PGE2, significantly improved osteoblasts differentiation on the 3D scaffolds. Importantly, EP4A significantly inhibited the tumor necrosis factor-alpha protein (TNF alpha), a key inflammatory cytokine, expression in macrophage cells, and largely rescued TNF alpha-suppressed alkaline phosphatase (ALP) activity in vitro. Surprisingly, BMP2-induced bone formation on the 3D scaffolds was significantly inhibited by EP4A after 4-week transplantation. These results indicated the complicity of the role of PGE2/EP4A-modulated TNF alpha expression and subsequent bone regeneration. Therefore, our study strongly suggests that substantial studies are essential before PGE2/EP4A can be developed as a new therapeutic because the closely related inflammation and osteogenesis are required to be coordinately regulated for bone regeneration.
Details
- Title: Subtitle
- Prostaglandin E2 Modulates Bone Morphogenetic Protein-2 Induced Osteogenic Differentiation on a Biomimetic 3D Nanofibrous Scaffold
- Creators
- Yangxi Liu - University of South DakotaQingqing Yao - University of South DakotaHongli Sun - University of South Dakota
- Resource Type
- Journal article
- Publication Details
- Journal of biomedical nanotechnology, Vol.14(4), pp.747-755
- DOI
- 10.1166/jbn.2018.2490
- PMID
- 31352948
- NLM abbreviation
- J Biomed Nanotechnol
- ISSN
- 1550-7033
- eISSN
- 1550-7041
- Publisher
- Amer Scientific Publishers
- Number of pages
- 9
- Grant note
- State of South Dakota P20 GM103620; P20 GM103548 / National Institutes of Health COBRE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA UP1500172 / South Dakota Board of Regents Competitive Research Grant (CRG) LQ15H180003 / Zhejiang National Nature Science Foundations 31600773 / Chinese National Nature Science Foundation; National Natural Science Foundation of China (NSFC) IIA-1355423 / National Science Foundation/EPSCoR Cooperative Agreement; National Science Foundation (NSF)
- Language
- English
- Date published
- 04/01/2018
- Academic Unit
- Roy J. Carver Department of Biomedical Engineering; Craniofacial Anomalies Research Center; Oral and Maxillofacial Surgery
- Record Identifier
- 9984367721902771
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