title: Identifying novel genes involved in both deer physiological and human pathological osteoporosis.
abstract: 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.
authors.affiliation: Department of Genetics, Eötvös Loránd University, Pázmány Péter s. 1/c, 1117, Budapest, Hungary.
authors.forename: Adrienn
authors.initials: A
authors.lastname: Borsy
authors.forename: János
authors.initials: J
authors.lastname: Podani
authors.forename: Viktor
authors.initials: V
authors.lastname: Stéger
authors.forename: Bernadett
authors.initials: B
authors.lastname: Balla
authors.forename: Arnold
authors.initials: A
authors.lastname: Horváth
authors.forename: János P
authors.initials: JP
authors.lastname: Kósa
authors.forename: István
authors.initials: I
authors.lastname: Gyurján
authors.forename: Andrea
authors.initials: A
authors.lastname: Molnár
authors.forename: Zoltán
authors.initials: Z
authors.lastname: Szabolcsi
authors.forename: László
authors.initials: L
authors.lastname: Szabó
authors.forename: Eéna
authors.initials: E
authors.lastname: Jakó
authors.forename: Zoltán
authors.initials: Z
authors.lastname: Zomborszky
authors.forename: János
authors.initials: J
authors.lastname: Nagy
authors.forename: Szabolcs
authors.initials: S
authors.lastname: Semsey
authors.forename: Tibor
authors.initials: T
authors.lastname: Vellai
authors.forename: Péter
authors.initials: P
authors.lastname: Lakatos
authors.forename: László
authors.initials: L
authors.lastname: Orosz
mesh_terms: 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
chemical_list: D051153:Wnt Proteins; D004247:DNA