COL1A1 and miR-29b show lower expression levels during osteoblast differentiation of bone marrow stromal cells from Osteogenesis Imperfecta patients

BMC Medical Genetics

Wilson A Silva⁴  Francisco JA de Paula³  João M Pina Neto²  Karen L Prata⁴  Dalila L Zanette⁴  Patrícia SP Lima¹  Carla M Kaneto⁵ 

[1] Department of Natural Science, Universidade Estadual do Sudoeste da Bahia, Vitória da Conquista, Bahia, Brazil;Department of Genetics, Medical School of Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, São Paulo, Brazil;Department of Clinical Medicine, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, São Paulo, Brazil;Regional Blood Center of Ribeirão Preto and National Institute of Science and Technology in Cell Therapy, Ribeirão Preto, Brazil;Department of Biological Science, Universidade Estadual de Santa Cruz – UESC - Ilhéus, Rodovia Jorge Amado, Km16, 45662-900 Ilhéus, BA, Brazil

关键词: Mesenchymalstem cells;    Osteogenesis;    COL1A1;    miR-29b;    Osteogenesis Imperfecta;   

Others  :  1092084
DOI  :  10.1186/1471-2350-15-45

 received in 2013-12-03, accepted in 2014-04-17,  发布年份 2014

【 摘 要 】

Background

The majority of Osteogenesis Imperfecta (OI) cases are caused by mutations in one of the two genes, COL1A1 and COL1A2 encoding for the two chains that trimerize to form the procollagen 1 molecule. However, alterations in gene expression and microRNAs (miRNAs) are responsible for the regulation of cell fate determination and may be evolved in OI phenotype.

Methods

In this work, we analyzed the coding region and intron/exon boundaries of COL1A1 and COL1A2 genes by sequence analysis using an ABI PRISM 3130 automated sequencer and Big Dye Terminator Sequencing protocol. COL1A1 and miR-29b expression were also evaluated during the osteoblastic differentiation of mesenchymal stem cell (MSC) by qRT-PCR using an ABI7500 Sequence Detection System.

Results

We have identified eight novel mutations, where of four may be responsible for OI phenotype. COL1A1 and miR-29b showed lower expression values in OI type I and type III samples. Interestingly, one type III OI sample from a patient with Bruck Syndrome showed COL1A1 and miR-29b expressions alike those from normal samples.

Conclusions

Results suggest that the miR-29b mechanism directed to regulate collagen protein accumulation during mineralization is dependent upon the amount of COL1A1 mRNA. Taken together, results indicate that the lower levels observed in OI samples were not sufficient for the induction of miR-29b.

【 授权许可】

   
2014 Kaneto et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

Figure 2.

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