Lim Mineralization Protein 3 Induces the Osteogenic Differentiation of Human Amniotic Fluid Stromal Cells through Kruppel-Like Factor-4 Downregulation and Further Bone-Specific Gene Expression

Lim Mineralization Protein 3 Induces the Osteogenic Differentiation of Human Amniotic Fluid Stromal Cells through Kruppel-Like Factor-4 Downregulation and Further Bone-Specific Gene Expression

Multipotent mesenchymal stem cells with extensive self-renewal properties can be easily isolated and rapidly expanded in culture from small volumes of amniotic fluid. These cells, namely, amniotic fluid-stromal cells (AFSCs), can be regarded as an attractive source for tissue engineering purposes, b...

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Main Authors: Marta Barba, Filomena Pirozzi, Nathalie Saulnier, Tiziana Vitali, Maria Teresa Natale, Giandomenico Logroscino, Paul D. Robbins, Andrea Gambotto, Giovanni Neri, Fabrizio Michetti, Enrico Pola, Wanda Lattanzi
Format: Article
Language:English
Published: Hindawi Limited 2012-01-01
Series:Journal of Biomedicine and Biotechnology
Online Access:http://dx.doi.org/10.1155/2012/813894
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spelling doaj-4821c8ba14a24dc99dd9ac622ca23ab92020-11-25T02:00:21ZengHindawi LimitedJournal of Biomedicine and Biotechnology1110-72431110-72512012-01-01201210.1155/2012/813894813894Lim Mineralization Protein 3 Induces the Osteogenic Differentiation of Human Amniotic Fluid Stromal Cells through Kruppel-Like Factor-4 Downregulation and Further Bone-Specific Gene ExpressionMarta Barba0Filomena Pirozzi1Nathalie Saulnier2Tiziana Vitali3Maria Teresa Natale4Giandomenico Logroscino5Paul D. Robbins6Andrea Gambotto7Giovanni Neri8Fabrizio Michetti9Enrico Pola10Wanda Lattanzi11Institute of Anatomy and Cell Biology, Università Cattolica del Sacro Cuore, L.go F. Vito 1, 00168 Rome, ItalyInstitute of Medical Genetics, Università Cattolica del Sacro Cuore, L.go F. Vito 1, 00168 Rome, ItalyInstitut National de la Santé et de la Recherche Medicale, 101 Rue de Tolbiac, 75654 Paris Cedex 13, FranceInstitute of Medical Genetics, Università Cattolica del Sacro Cuore, L.go F. Vito 1, 00168 Rome, ItalyInstitute of Medical Genetics, Università Cattolica del Sacro Cuore, L.go F. Vito 1, 00168 Rome, ItalyDepartment of Orthopaedics, Università Cattolica del Sacro Cuore, L.go Gemelli 8, 00168 Rome, ItalyDepartment of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, 427 Bridgeside Point II, 450 Technology Drive, Pittsburgh, PA 15219, USADepartment of Surgery, Rangos Research Center, University of Pittsburgh 530 45th Street, Pittsburgh, PA 15201, USAInstitute of Medical Genetics, Università Cattolica del Sacro Cuore, L.go F. Vito 1, 00168 Rome, ItalyInstitute of Anatomy and Cell Biology, Università Cattolica del Sacro Cuore, L.go F. Vito 1, 00168 Rome, ItalyDepartment of Orthopaedics, Università Cattolica del Sacro Cuore, L.go Gemelli 8, 00168 Rome, ItalyInstitute of Anatomy and Cell Biology, Università Cattolica del Sacro Cuore, L.go F. Vito 1, 00168 Rome, ItalyMultipotent mesenchymal stem cells with extensive self-renewal properties can be easily isolated and rapidly expanded in culture from small volumes of amniotic fluid. These cells, namely, amniotic fluid-stromal cells (AFSCs), can be regarded as an attractive source for tissue engineering purposes, being phenotypically and genetically stable, plus overcoming all the safety and ethical issues related to the use of embryonic/fetal cells. LMP3 is a novel osteoinductive molecule acting upstream to the main osteogenic pathways. This study is aimed at delineating the basic molecular events underlying LMP3-induced osteogenesis, using AFSCs as a cellular model to focus on the molecular features underlying the multipotency/differentiation switch. For this purpose, AFSCs were isolated and characterized in vitro and transfected with a defective adenoviral vector expressing the human LMP3. LMP3 induced the successful osteogenic differentiation of AFSC by inducing the expression of osteogenic markers and osteospecific transcription factors. Moreover, LMP3 induced an early repression of the kruppel-like factor-4, implicated in MSC stemness maintenance. KLF4 repression was released upon LMP3 silencing, indicating that this event could be reasonably considered among the basic molecular events that govern the proliferation/differentiation switch during LMP3-induced osteogenic differentiation of AFSC.http://dx.doi.org/10.1155/2012/813894
collection DOAJ
language English
format Article
sources DOAJ
author Marta Barba
Filomena Pirozzi
Nathalie Saulnier
Tiziana Vitali
Maria Teresa Natale
Giandomenico Logroscino
Paul D. Robbins
Andrea Gambotto
Giovanni Neri
Fabrizio Michetti
Enrico Pola
Wanda Lattanzi
spellingShingle Marta Barba
Filomena Pirozzi
Nathalie Saulnier
Tiziana Vitali
Maria Teresa Natale
Giandomenico Logroscino
Paul D. Robbins
Andrea Gambotto
Giovanni Neri
Fabrizio Michetti
Enrico Pola
Wanda Lattanzi
Lim Mineralization Protein 3 Induces the Osteogenic Differentiation of Human Amniotic Fluid Stromal Cells through Kruppel-Like Factor-4 Downregulation and Further Bone-Specific Gene Expression
Journal of Biomedicine and Biotechnology
author_facet Marta Barba
Filomena Pirozzi
Nathalie Saulnier
Tiziana Vitali
Maria Teresa Natale
Giandomenico Logroscino
Paul D. Robbins
Andrea Gambotto
Giovanni Neri
Fabrizio Michetti
Enrico Pola
Wanda Lattanzi
author_sort Marta Barba
title Lim Mineralization Protein 3 Induces the Osteogenic Differentiation of Human Amniotic Fluid Stromal Cells through Kruppel-Like Factor-4 Downregulation and Further Bone-Specific Gene Expression
title_short Lim Mineralization Protein 3 Induces the Osteogenic Differentiation of Human Amniotic Fluid Stromal Cells through Kruppel-Like Factor-4 Downregulation and Further Bone-Specific Gene Expression
title_full Lim Mineralization Protein 3 Induces the Osteogenic Differentiation of Human Amniotic Fluid Stromal Cells through Kruppel-Like Factor-4 Downregulation and Further Bone-Specific Gene Expression
title_fullStr Lim Mineralization Protein 3 Induces the Osteogenic Differentiation of Human Amniotic Fluid Stromal Cells through Kruppel-Like Factor-4 Downregulation and Further Bone-Specific Gene Expression
title_full_unstemmed Lim Mineralization Protein 3 Induces the Osteogenic Differentiation of Human Amniotic Fluid Stromal Cells through Kruppel-Like Factor-4 Downregulation and Further Bone-Specific Gene Expression
title_sort lim mineralization protein 3 induces the osteogenic differentiation of human amniotic fluid stromal cells through kruppel-like factor-4 downregulation and further bone-specific gene expression
publisher Hindawi Limited
series Journal of Biomedicine and Biotechnology
issn 1110-7243
1110-7251
publishDate 2012-01-01
description Multipotent mesenchymal stem cells with extensive self-renewal properties can be easily isolated and rapidly expanded in culture from small volumes of amniotic fluid. These cells, namely, amniotic fluid-stromal cells (AFSCs), can be regarded as an attractive source for tissue engineering purposes, being phenotypically and genetically stable, plus overcoming all the safety and ethical issues related to the use of embryonic/fetal cells. LMP3 is a novel osteoinductive molecule acting upstream to the main osteogenic pathways. This study is aimed at delineating the basic molecular events underlying LMP3-induced osteogenesis, using AFSCs as a cellular model to focus on the molecular features underlying the multipotency/differentiation switch. For this purpose, AFSCs were isolated and characterized in vitro and transfected with a defective adenoviral vector expressing the human LMP3. LMP3 induced the successful osteogenic differentiation of AFSC by inducing the expression of osteogenic markers and osteospecific transcription factors. Moreover, LMP3 induced an early repression of the kruppel-like factor-4, implicated in MSC stemness maintenance. KLF4 repression was released upon LMP3 silencing, indicating that this event could be reasonably considered among the basic molecular events that govern the proliferation/differentiation switch during LMP3-induced osteogenic differentiation of AFSC.
url http://dx.doi.org/10.1155/2012/813894
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