[Changes of gene expression and its role in pathogenesis in fibrous and non-fibrous dysplastic bone tissues in women].
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.


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.
Kiss
János
J
Semmelweis Egyetem, Altalános Orvostudományi Kar Ortopédiai Klinika Budapest Karolina út 27. 1113. dysplasia.drkiss61@googlemail.com
Balla
Bernadett
B
Kósa
P János
PJ
Borsy
Adrienn
A
Podani
János
J
Takács
István
I
Lazáry
Aron
A
Nagy
Zsolt
Z
Bácsi
Krisztián
K
Szlávy
Eszter
E
Szendrôi
Miklós
M
Speer
Gábor
G
Orosz
László
L
Lakatos
Péter
P
D000328:Adult; D019485:Bone Morphogenetic Proteins / Q000235:genetics* / Q000378:metabolism*; D001842:Bone and Bones / Q000378:metabolism* / Q000473:pathology*; D016002:Discriminant Analysis; D005260:Female; D005357:Fibrous Dysplasia of Bone / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D006801:Humans; D008875:Middle Aged; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
D019485:Bone Morphogenetic Proteins; D012333:RNA, Messenger