Identifying novel genes involved in both deer physiological and human pathological osteoporosis.
Osteoporosis attacks 10% of the population worldwide. Humans or even the model animals of the disease cannot recover from porous bone. Regeneration in skeletal elements is the unique feature of our newly investigated osteoporosis model, the red deer (Cervus elaphus) stag. Cyclic physiological osteoporosis is a consequence of the annual antler cycle. This phenomenon raises the possibility to identify genes involved in the regulation of bone mineral density on the basis of comparative genomics between deer and human. We compare gene expression activity of osteoporotic and regenerating rib bone samples versus autumn dwell control in red deer by microarray hybridization. Identified genes were tested on human femoral bone tissue from non-osteoporotic controls and patients affected with age-related osteoporosis. Expression data were evaluated by Principal Components Analysis and Canonical Variates Analysis. Separation of patients into a normal and an affected group based on ten formerly known osteoporosis reference genes was significantly improved by expanding the data with newly identified genes. These genes include IGSF4, FABP3, FABP4, FKBP2, TIMP2, TMSB4X, TRIB, and members of the Wnt signaling. This study supports that extensive comparative genomic analyses, here deer and human, provide a novel approach to identify new targets for human diagnostics and therapy.
Borsy
Adrienn
A
Department of Genetics, Eötvös Loránd University, Pázmány Péter s. 1/c, 1117, Budapest, Hungary.
Podani
János
J
Stéger
Viktor
V
Balla
Bernadett
B
Horváth
Arnold
A
Kósa
János P
JP
Gyurján
István
I
Molnár
Andrea
A
Szabolcsi
Zoltán
Z
Szabó
László
L
Jakó
Eéna
E
Zomborszky
Zoltán
Z
Nagy
János
J
Semsey
Szabolcs
S
Vellai
Tibor
T
Lakatos
Péter
P
Orosz
László
L
D000368:Aged; D000818:Animals; D015519:Bone Density / Q000235:genetics*; D001861:Bone Regeneration / Q000235:genetics*; D016022:Case-Control Studies; D004247:DNA / Q000235:genetics; D003670:Deer / Q000235:genetics* / Q000502:physiology*; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D020411:Oligonucleotide Array Sequence Analysis; D015663:Osteoporosis, Postmenopausal / Q000235:genetics* / Q000503:physiopathology*; D025341:Principal Component Analysis; D013045:Species Specificity; D051153:Wnt Proteins / Q000235:genetics
D051153:Wnt Proteins; D004247:DNA