Different gene expression patterns in the bone tissue of aging postmenopausal osteoporotic and non-osteoporotic women.
OBJECTIVE
To identify genes that are differently expressed in osteoporotic and non-osteoporotic human bone and to describe the relationships between these genes using multivariate data analysis.


METHODS
Seven bone tissue samples from postmenopausal osteoporotic patients and 10 bone tissue samples from postmenopausal non-osteoporotic women were examined in our study. Messenger RNA was prepared from each sample and reverse transcribed to cDNA. The expression differences of 87 selected genes were analyzed in a Taqman probe-based quantitative real-time RT-PCR system.


RESULTS
A Mann-Whitney U-test indicated significant differences in the expression of nine genes (p < or = 0.05). Seven of these nine genes-ALPL, COL1A1, MMP2, MMP13, MMP9, PDGFA, NFKB1-were significantly downregulated in the bone tissue of osteoporotic women, while CD36 and TWIST2 were significantly upregulated in osteoporotic patients. Principal components analysis was used to evaluate data structure and the relationship between osteoporotic and non-osteoporotic phenotypes based on the multiple mRNA expression profiles of 78 genes. Canonical variates analysis demonstrated further that osteoporotic and non-osteoporotic tissues can be distinguished by expression analysis of genes coding growth factors/non-collagen matrix molecules, and genes belonging to the canonical TGFB pathway.


CONCLUSIONS
Significant differences observed in gene expression profiles of osteoporotic and non-osteoporotic human bone tissues provide further insight into the pathogenesis of this disease. Characterization of the differences between osteoporotic and non-osteoporotic bones by expression profiling will contribute to the development of diagnostic tools in the future.
Balla
Bernadett
B
1st Department of Internal Medicine, Semmelweis University, Korányi S. u. 2/a, Budapest, 1083, Hungary. betti@bel1.sote.hu
Kósa
János P
JP
Kiss
János
J
Borsy
Adrienn
A
Podani
János
J
Takács
István
I
Lazáry
Aron
A
Nagy
Zsolt
Z
Bácsi
Krisztián
K
Speer
Gábor
G
Orosz
László
L
Lakatos
Péter
P
D000368:Aged; D000375:Aging / Q000235:genetics* / Q000378:metabolism; D001842:Bone and Bones / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D015536:Down-Regulation / Q000235:genetics; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000235:genetics*; D014644:Genetic Variation / Q000235:genetics; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism; D008875:Middle Aged; D015999:Multivariate Analysis; D015663:Osteoporosis, Postmenopausal / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D025341:Principal Component Analysis; D011506:Proteins / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation / Q000235:genetics
D036341:Intercellular Signaling Peptides and Proteins; D011506:Proteins; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta