Small molecule-mediated tribbles homolog 3 promotes bone formation induced by bone morphogenetic protein-2

Abstract Although bone morphogenetic protein-2 (BMP2) has demonstrated extraordinary potential in bone formation, its clinical applications require supraphysiological milligram-level doses that increase postoperative inflammation and inappropriate adipogenesis, resulting in well-documented life-thre...

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Autores principales:	Jiabing Fan, Joan Pi-Anfruns, Mian Guo, Dan C. S. Im, Zhong-Kai Cui, Soyon Kim, Benjamin M. Wu, Tara L. Aghaloo, Min Lee
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/9801fe39bc0641a2ad11f8e394d6e216
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spelling	oai:doaj.org-article:9801fe39bc0641a2ad11f8e394d6e2162021-12-02T12:32:29ZSmall molecule-mediated tribbles homolog 3 promotes bone formation induced by bone morphogenetic protein-210.1038/s41598-017-07932-z2045-2322https://doaj.org/article/9801fe39bc0641a2ad11f8e394d6e2162017-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-07932-zhttps://doaj.org/toc/2045-2322Abstract Although bone morphogenetic protein-2 (BMP2) has demonstrated extraordinary potential in bone formation, its clinical applications require supraphysiological milligram-level doses that increase postoperative inflammation and inappropriate adipogenesis, resulting in well-documented life-threatening cervical swelling and cyst-like bone formation. Recent promising alternative biomolecular strategies are toward promoting pro-osteogenic activity of BMP2 while simultaneously suppressing its adverse effects. Here, we demonstrated that small molecular phenamil synergized osteogenesis and bone formation with BMP2 in a rat critical size mandibular defect model. Moreover, we successfully elicited the BMP2 adverse outcomes (i.e. adipogenesis and inflammation) in the mandibular defect by applying high dose BMP2. Phenamil treatment significantly improves the quality of newly formed bone by inhibiting BMP2 induced fatty cyst-like structure and inflammatory soft-tissue swelling. The observed positive phenamil effects were associated with upregulation of tribbles homolog 3 (Trib3) that suppressed adipogenic differentiation and inflammatory responses by negatively regulating PPARγ and NF-κB transcriptional activities. Thus, use of BMP2 along with phenamil stimulation or Trib3 augmentation may be a promising strategy to improve clinical efficacy and safety of current BMP therapeutics.Jiabing FanJoan Pi-AnfrunsMian GuoDan C. S. ImZhong-Kai CuiSoyon KimBenjamin M. WuTara L. AghalooMin LeeNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-13 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Jiabing Fan Joan Pi-Anfruns Mian Guo Dan C. S. Im Zhong-Kai Cui Soyon Kim Benjamin M. Wu Tara L. Aghaloo Min Lee Small molecule-mediated tribbles homolog 3 promotes bone formation induced by bone morphogenetic protein-2
description	Abstract Although bone morphogenetic protein-2 (BMP2) has demonstrated extraordinary potential in bone formation, its clinical applications require supraphysiological milligram-level doses that increase postoperative inflammation and inappropriate adipogenesis, resulting in well-documented life-threatening cervical swelling and cyst-like bone formation. Recent promising alternative biomolecular strategies are toward promoting pro-osteogenic activity of BMP2 while simultaneously suppressing its adverse effects. Here, we demonstrated that small molecular phenamil synergized osteogenesis and bone formation with BMP2 in a rat critical size mandibular defect model. Moreover, we successfully elicited the BMP2 adverse outcomes (i.e. adipogenesis and inflammation) in the mandibular defect by applying high dose BMP2. Phenamil treatment significantly improves the quality of newly formed bone by inhibiting BMP2 induced fatty cyst-like structure and inflammatory soft-tissue swelling. The observed positive phenamil effects were associated with upregulation of tribbles homolog 3 (Trib3) that suppressed adipogenic differentiation and inflammatory responses by negatively regulating PPARγ and NF-κB transcriptional activities. Thus, use of BMP2 along with phenamil stimulation or Trib3 augmentation may be a promising strategy to improve clinical efficacy and safety of current BMP therapeutics.
format	article
author	Jiabing Fan Joan Pi-Anfruns Mian Guo Dan C. S. Im Zhong-Kai Cui Soyon Kim Benjamin M. Wu Tara L. Aghaloo Min Lee
author_facet	Jiabing Fan Joan Pi-Anfruns Mian Guo Dan C. S. Im Zhong-Kai Cui Soyon Kim Benjamin M. Wu Tara L. Aghaloo Min Lee
author_sort	Jiabing Fan
title	Small molecule-mediated tribbles homolog 3 promotes bone formation induced by bone morphogenetic protein-2
title_short	Small molecule-mediated tribbles homolog 3 promotes bone formation induced by bone morphogenetic protein-2
title_full	Small molecule-mediated tribbles homolog 3 promotes bone formation induced by bone morphogenetic protein-2
title_fullStr	Small molecule-mediated tribbles homolog 3 promotes bone formation induced by bone morphogenetic protein-2
title_full_unstemmed	Small molecule-mediated tribbles homolog 3 promotes bone formation induced by bone morphogenetic protein-2
title_sort	small molecule-mediated tribbles homolog 3 promotes bone formation induced by bone morphogenetic protein-2
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/9801fe39bc0641a2ad11f8e394d6e216
work_keys_str_mv	AT jiabingfan smallmoleculemediatedtribbleshomolog3promotesboneformationinducedbybonemorphogeneticprotein2 AT joanpianfruns smallmoleculemediatedtribbleshomolog3promotesboneformationinducedbybonemorphogeneticprotein2 AT mianguo smallmoleculemediatedtribbleshomolog3promotesboneformationinducedbybonemorphogeneticprotein2 AT dancsim smallmoleculemediatedtribbleshomolog3promotesboneformationinducedbybonemorphogeneticprotein2 AT zhongkaicui smallmoleculemediatedtribbleshomolog3promotesboneformationinducedbybonemorphogeneticprotein2 AT soyonkim smallmoleculemediatedtribbleshomolog3promotesboneformationinducedbybonemorphogeneticprotein2 AT benjaminmwu smallmoleculemediatedtribbleshomolog3promotesboneformationinducedbybonemorphogeneticprotein2 AT taralaghaloo smallmoleculemediatedtribbleshomolog3promotesboneformationinducedbybonemorphogeneticprotein2 AT minlee smallmoleculemediatedtribbleshomolog3promotesboneformationinducedbybonemorphogeneticprotein2
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Small molecule-mediated tribbles homolog 3 promotes bone formation induced by bone morphogenetic protein-2

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