Please use this identifier to cite or link to this item: https://www.arca.fiocruz.br/handle/icict/18390
Title: Osteoblastic differentiation of bone marrow mesenchymal stromal cells in Bruck Syndrome
Authors: Kaneto, Carla Martins
Lima, Patrícia Santos Pereira
Zanette, Dalila Lucíola
Oliveira, Thiago Yukio Kikuchi
Pereira, Francisco de Assis
Lorenzi, Julio Cesar Cetrulo
Santos, Jane Lima dos
Prata, Karen L
Pina Neto, João Monteiro de
Paula, Francisco José Albuquerque de
Silva Junior, Wilson Araújo da
Affilliation: Universidade de São Paulo. Escola Medica de Ribeirão Preto. Departamento de Genetica. Ribeirão Preto, SP, Brasil / Universidade Estadual de Santa Cruz. Biological Science. Ilheus, BA, Brazil
Universidade Estadual do Sudoeste da Bahia. Department of Natural Science. Vitória da Conquista, BA, Brazil
Universidade de São Paulo. Escola Medica de Ribeirão Preto. Departamento de Genética. Ribeirão Preto, SP, Brasil / National Institute of Science and Technology in Cell Therapy. Regional Blood Center of Ribeirão Preto. Ribeirão Preto, SP, Brazil
The Rockefeller University. Laboratory of Molecular Immunology. New York, NY, USA
Universidade Federal de Sergipe. Department of Internal Medicine and Pathology. Aracaju, SE, Brazil
The Rockefeller University. Laboratory of Molecular Immunology. New York, NY, USA
Universidade Estadual de Santa Cruz. Biological Science. Ilheus, BA, Brazil
National Institute of Science and Technology in Cell Therapy. Regional Blood Center of Ribeirão Preto. Ribeirão Preto, SP, Brazil
Universidade de São Paulo. Escola Medica de Ribeirão Preto. Departamento de Genética. Ribeirão Preto, SP, Brasil
Universidade de São Paulo. Faculdade de Medicina de Ribeirão Preto. Department of Clinical Medicine. Ribeirão Preto, SP, Brazil
Universidade de São Paulo. Escola Medica de Ribeirão Preto. Departamento de Genética. Ribeirão Preto, SP, Brasil / Universidade Estadual de Santa Cruz. Biological Science. Ilheus, BA, Brazil
Abstract: Osteogenesis Imperfecta (OI) (OMIM %259450) is a heterogeneous group of inherited disorders characterized by increased bone fragility, with clinical severity ranging from mild to lethal. The majority of OI cases are caused by mutations in COL1A1 or COL1A2. Bruck Syndrome (BS) is a further recessively-inherited OI-like phenotype in which bone fragility is associated with the unusual finding of pterygia and contractures of the large joints. Notably, several studies have failed to show any abnormalities in the biosynthesis of collagen 1 in BS patientes. Evidence was obtained for a specific defect of the procollagen telopeptide lysine hydroxylation in BS, whereas mutations in the gene PLOD2 have been identified. Recently, several studies described FKBP10 mutations in OI-like and BS patients, suggesting that FKBP10 is a bonafide BS locus. Methods: We analyzed the coding region and intron/exon boundaries of COL1A1, COL1A2, PLOD2 and FKBP10 genes by sequence analysis using an ABI PRISM 3130 automated sequencer and Big Dye Terminator Sequencing protocol. Mononuclear cells obtained from the bone marrow of BS, OI patients and healthy donors were cultured and osteogenic differentiation was induced. The gene expression of osteoblast specific markers were also evaluated during the osteoblastic differentiation of mesenchymal stem cell (MSC) by qRT-PCR using an ABI7500 Sequence Detection System. Results: No mutations in COL1A1, COL1A2 or PLOD2 were found in BS patient. We found a homozygous 1-base-pair duplication (c.831dupC) that is predicted to produce a translational frameshift mutation and a premature protein truncation 17 aminoacids downstream (p.Gly278ArgfsX95). The gene expression of osteoblast specific markers BGLAP, COL1A1, MSX2, SPARC and VDR was evaluated by Real Time RT-PCR during differentiation into osteoblasts and results showed similar patterns of osteoblast markers expression in BS and healthy controls. On the other hand, when compared with OI patients, the expression pattern of these genes was found to be different. Conclusions: Our work suggests that the gene expression profiles observed during mesenchymal stromal cell differentiation into osteoblast are distinct in BS patients as compared to OI patients. The present study shows for the first time that genes involved in osteogenesis are differentially expressed in BS and OI patients
Keywords: Bruck syndrome
Osteogenesis Imperfecta
Bone marrow mesenchymal stromal cell
Osteogenic differentiation
Gene expression
keywords: Sindrome de Bruck
Osteogênese
Célula estromal mesenquimal da medula óssea
Diferenciação osteogénica
Expressão génica
Issue Date: 2016
Publisher: BioMed Central
Citation: CANETO, C. M. et al. Osteoblastic differentiation of bone marrow mesenchymal stromal cells in Bruck Syndrome. BMC Medical Genetics, v. 17, p. 38, 2016.
Description: Zanette, D. L. Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil “Documento produzido em parceria ou por autor vinculado à Fiocruz, mas não consta à informação no documento”.
DOI: 10.1186/s12881-016-0301-7
ISSN: 1471-2350
Copyright: open access
Appears in Collections:BA - IGM - Artigos de Periódicos

Files in This Item:
File Description SizeFormat 
Kaneto CM Osteoblastic differentiation....pdf1.42 MBAdobe PDFView/Open
Kaneto CM Osteoblastic differentiation....pdf1.42 MBAdobe PDFView/Open


FacebookTwitterDeliciousLinkedInGoogle BookmarksBibTex Format mendeley Endnote DiggMySpace

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.