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.

Antler development and coupled osteoporosis in the skeleton of red deer Cervus elaphus: expression dynamics for regulatory and effector genes

“…Bar 3 mm. (For more information see "Materials and methods", ESM Figure S1 and Borsy et al 2009) Skeletal bone samples Ribs and vertebras removed from the killed Stag 1 were extensively washed in PBS for eliminating blood and marrow contamination and then immediately frozen in liquid nitrogen. Both the inner part of the ribs and the body of the vertebras displayed an extremely porotic and fragile bone structure in the stag having velvet antlers (see Fig.…”

“…Previously we identiWed a set of genes which are diVerentially expressed during the rapid but controlled tissue proliferation (Korpos et al 2005;Molnar et al 2007;Gyurján et al 2007;Villányi et al 2008) and another set, which is involved in the skeletal physiological osteoporosis (Borsy et al 2009). In this work, we developed an antlerspeciWc cDNA microarray in order to compare gene expression levels in the tissues of the mineralizing velvet antler and the skeleton (ribs and vertebra) of deer stags.…”

“…As a consequence, the gap is Wlled by mobilizing minerals from the skeleton, thus causing a temporary bone loss termed cyclic physiological osteoporosis (Banks et al 1968a, b;Chapman et al 1975). This phenomenon resembles human (pathological) osteoporosis both in its visual appearance and in its genetic background (Borsy et al 2009). Before the rutting season, during the Wtness recovery period in July and August, the process is reversed and bone mineral density (BMD) is restored.…”

Gene Expression Changes in Femoral Head Necrosis of Human Bone Tissue

“…For comparing gene expression patterns in the bone tissue of ONFH and non-ONFH subjects, we selected 117 genes based on recent literature (Supplementary table), OMIM (Online Mendelian Inheritance in Man) database, as well as our data regarding genetic pathway analysis [6,[9][10][11]. Twenty seven genes from the common TGF-beta/BMP pathway and Wingless (Wnt) cascade were selected for these studies; further 23 genes from extracellular matrix (ECM) components, 8 are involved in ECM degradation, 9 genes code growth factors, 5 genes code cell adhesion molecules, 7 genes code transcriptional factors and 12 of them are known to be controlled by estrogen and the 26 remaining genes were assorted by our previous published analyses [6,[9][10][11].…”

Drosophila Orthologs, expressed specifically in Courting Zebra Finch Males, are engaged in Courtshipe

“…Comparative genomic approaches represent successful strategies to explore the genes and gene networks behind an interesting biological phenomenon. For example, several candidate genes behind human osteoporosis were revealed by comparing the transcriptomes of red deer (Cervus elaphus) osteoporotic and regenerating rib bone samples [4,5]. In the present study we followed the experimental strategy above, and made use of the plaque-based competitive hybridization (PBCH) technique which was successfully used to identify e.g.…”