Gene expression patterns in the bone tissue of women with fibrous dysplasia.
Fibrous dysplasia is an isolated skeletal disorder caused by a somatic activating mutation of GNAS gene with abnormal unmineralized matrix overproduction and extensive undifferentiated bone cell accumulation in the fibro-osseous lesions. The aim of our investigation was to identify genes that are differently expressed in fibrous versus non-fibrous human bone and to describe the relationships between these genes using multivariate data analysis. Six bone tissue samples from female patients with fibrous dysplastia (FD) and seven bone tissue samples from women without FD (non-FD) were examined. The expression differences of selected 118 genes were analyzed by the TaqMan probe-based quantitative real-time RT-PCR system. The Mann-Whitney U-test indicated marked differences in the expression of 22 genes between FD and non-FD individuals. Nine genes were upregulated in FD women compared to non-FD ones and 18 genes showed a downregulated pattern. These altered genes code for minor collagen molecules, extracellular matrix digesting enzymes, transcription factors, adhesion molecules, growth factors, pro-inflammatory cytokines, and lipid metabolism-affected substrates. Canonical variates analysis demonstrated that FD and non-FD 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. The remarkable changed gene expression profile observed in the fibrous dysplastic human bone tissue may provide further insight into the pathogenetic process of fibrous degeneration of bone.
Kiss
János
J
Department of Orthopaedics, Semmelweis University, Budapest, Hungary.
Balla
Bernadett
B
Kósa
János P
JP
Borsy
Adrienn
A
Podani
János
J
Takács
István
I
Lazáry
Aron
A
Nagy
Zsolt
Z
Bácsi
Krisztián
K
Kis
Adrián
A
Szlávy
Eszter
E
Szendroi
Miklós
M
Speer
Gábor
G
Orosz
László
L
Lakatos
Péter
P
D000328:Adult; D019485:Bone Morphogenetic Proteins / Q000235:genetics; D001842:Bone and Bones; D016022:Case-Control Studies; D005109:Extracellular Matrix / Q000235:genetics; D005260:Female; D005357:Fibrous Dysplasia of Bone / Q000235:genetics*; D019204:GTP-Binding Proteins; D020869:Gene Expression Profiling / Q000379:methods*; D005786:Gene Expression Regulation; D006801:Humans; D008875:Middle Aged; D015999:Multivariate Analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction
D019485:Bone Morphogenetic Proteins; D019204:GTP-Binding Proteins