A génexpresszió változásai és patogenetikai jelentoségük fibrosus dysplasiás és nem fibrosus dysplasiás nok csontszövetében

Translated title of the contribution: Changes of gene expression and its role in pathogenesis in fibrous and non-fibrous dysplastic bone tissues in women

János Kiss, Bernadett Balla, J. Kósa, Adrienn Borsy, J. Podaní, I. Takács, Áron Lazáry, Zsolt Nagy, Krisztián Bácsi, Eszter Szlávy, M. Szendrői, G. Speer, L. Orosz, P. Lakatos

Research output: Contribution to journalArticle

Abstract

Fibrous dysplasia is an isolated skeletal disorder caused by a somatic activating mutation of GNAS1 gene with abnormal unmineralized matrix overproduction and extensive undifferentiated bone cell accumulation in fibro-osseous lesions. The aim of the investigation was to identify genes that are differently expressed in fibrous vs. non-fibrous human bone and to describe the relationships between these genes using multivariate data analysis. Materials and Methods: Six bone tissue samples from fibrous dysplastic female patients and 7 bone tissue samples from non-fibrous dysplastic women were examined. The 6 female fibrous samples were taken from the fibrous dysplastic lesion itself while the control samples of 7 non-fibrous dysplastic females were taken from the femoral neck during the hip replacement procedure. The expression differences of selected 118 genes were analyzed in TaqMan probe based quantitative real-time RT-PCR system. Results: The Mann-Whitney U test indicated significant differences in the expression of 27 genes of fibrous dysplasial and non fibrous dysplasial individuals (p ≤ 0.05). Nine genes were significantly up-regulated in fibrous dysplasial women compared to non fibrous dysplasial ones and eighteen genes showed a down-regulated pattern. These significantly altered genes coding for minor collagen molecules, extracellular matrix digesting enzymes, transcription factors, adhesion molecules, growth factors, pro-inflammatory cytokines and lipid metabolism-affected substrates. Canonical variety analysis demonstrated that fibrous dysplastic and non fibrous dysplastic bone tissues can be distinguished by the multiple expression profile analysis of numerous genes controlled via a G-protein coupled pathway and BMP cascade as well as genes coding for extracellular matrix composing molecules. Conclusions: The significantly altered gene expression profile observed in the fibrous dysplastic human bone tissue may provide further insight into the pathogenetic process of fibrous degeneration of bone.

Original languageHungarian
Pages (from-to)1656-1665
Number of pages10
JournalOrvosi Hetilap
Volume151
Issue number40
DOIs
Publication statusPublished - Oct 1 2010

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Gene Expression
Bone and Bones
Genes
Extracellular Matrix
Femur Neck
Nonparametric Statistics
Lipid Metabolism
Transcriptome
GTP-Binding Proteins
Hip
Real-Time Polymerase Chain Reaction
Intercellular Signaling Peptides and Proteins
Transcription Factors
Collagen
Multivariate Analysis
Cytokines
Mutation
Enzymes

ASJC Scopus subject areas

  • Medicine(all)

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A génexpresszió változásai és patogenetikai jelentoségük fibrosus dysplasiás és nem fibrosus dysplasiás nok csontszövetében. / Kiss, János; Balla, Bernadett; Kósa, J.; Borsy, Adrienn; Podaní, J.; Takács, I.; Lazáry, Áron; Nagy, Zsolt; Bácsi, Krisztián; Szlávy, Eszter; Szendrői, M.; Speer, G.; Orosz, L.; Lakatos, P.

In: Orvosi Hetilap, Vol. 151, No. 40, 01.10.2010, p. 1656-1665.

Research output: Contribution to journalArticle

Kiss, János ; Balla, Bernadett ; Kósa, J. ; Borsy, Adrienn ; Podaní, J. ; Takács, I. ; Lazáry, Áron ; Nagy, Zsolt ; Bácsi, Krisztián ; Szlávy, Eszter ; Szendrői, M. ; Speer, G. ; Orosz, L. ; Lakatos, P. / A génexpresszió változásai és patogenetikai jelentoségük fibrosus dysplasiás és nem fibrosus dysplasiás nok csontszövetében. In: Orvosi Hetilap. 2010 ; Vol. 151, No. 40. pp. 1656-1665.
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AU - Balla, Bernadett

AU - Kósa, J.

AU - Borsy, Adrienn

AU - Podaní, J.

AU - Takács, I.

AU - Lazáry, Áron

AU - Nagy, Zsolt

AU - Bácsi, Krisztián

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N2 - Fibrous dysplasia is an isolated skeletal disorder caused by a somatic activating mutation of GNAS1 gene with abnormal unmineralized matrix overproduction and extensive undifferentiated bone cell accumulation in fibro-osseous lesions. The aim of the investigation was to identify genes that are differently expressed in fibrous vs. non-fibrous human bone and to describe the relationships between these genes using multivariate data analysis. Materials and Methods: Six bone tissue samples from fibrous dysplastic female patients and 7 bone tissue samples from non-fibrous dysplastic women were examined. The 6 female fibrous samples were taken from the fibrous dysplastic lesion itself while the control samples of 7 non-fibrous dysplastic females were taken from the femoral neck during the hip replacement procedure. The expression differences of selected 118 genes were analyzed in TaqMan probe based quantitative real-time RT-PCR system. Results: The Mann-Whitney U test indicated significant differences in the expression of 27 genes of fibrous dysplasial and non fibrous dysplasial individuals (p ≤ 0.05). Nine genes were significantly up-regulated in fibrous dysplasial women compared to non fibrous dysplasial ones and eighteen genes showed a down-regulated pattern. These significantly altered genes coding for minor collagen molecules, extracellular matrix digesting enzymes, transcription factors, adhesion molecules, growth factors, pro-inflammatory cytokines and lipid metabolism-affected substrates. Canonical variety analysis demonstrated that fibrous dysplastic and non fibrous dysplastic bone tissues can be distinguished by the multiple expression profile analysis of numerous genes controlled via a G-protein coupled pathway and BMP cascade as well as genes coding for extracellular matrix composing molecules. Conclusions: The significantly altered gene expression profile observed in the fibrous dysplastic human bone tissue may provide further insight into the pathogenetic process of fibrous degeneration of bone.

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