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Journal of Biomedicine and Biotechnology
Volume 2012 (2012), Article ID 813894, 11 pages
Research Article

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

1Institute of Anatomy and Cell Biology, Università Cattolica del Sacro Cuore, L.go F. Vito 1, 00168 Rome, Italy
2Institute of Medical Genetics, Università Cattolica del Sacro Cuore, L.go F. Vito 1, 00168 Rome, Italy
3Institut National de la Santé et de la Recherche Medicale, 101 Rue de Tolbiac, 75654 Paris Cedex 13, France
4Institut Cochin, Université Paris Descartes, Sorbonne Paris Descartes, CNRS (UMR 8104), Paris, France
5Department of Orthopaedics, Università Cattolica del Sacro Cuore, L.go Gemelli 8, 00168 Rome, Italy
6Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, 427 Bridgeside Point II, 450 Technology Drive, Pittsburgh, PA 15219, USA
7Department of Metabolism and Aging, The Scripps Research Institute-Florida, 130 Scripps Way, Jupiter, Florida 33458, USA
8Department of Surgery, Rangos Research Center, University of Pittsburgh 530 45th Street, Pittsburgh, PA 15201, USA
9Latium Musculoskeletal Tissue Bank, L.go F. Vito 1, Rome, Italy

Received 23 January 2012; Revised 19 April 2012; Accepted 30 April 2012

Academic Editor: Thomas Lufkin

Copyright © 2012 Marta Barba et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


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.