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Molecular Genetics and Genomics

, Volume 281, Issue 3, pp 301–313 | Cite as

Identifying novel genes involved in both deer physiological and human pathological osteoporosis

  • Adrienn Borsy
  • János Podani
  • Viktor Stéger
  • Bernadett Balla
  • Arnold Horváth
  • János P. Kósa
  • István GyurjánJr
  • Andrea Molnár
  • Zoltán Szabolcsi
  • László Szabó
  • Eéna Jakó
  • Zoltán Zomborszky
  • János Nagy
  • Szabolcs Semsey
  • Tibor Vellai
  • Péter Lakatos
  • László Orosz
Original Paper

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.

Keywords

Bone metabolism Interspecific microarray Gene expression pattern Real-time PCR 

Abbreviations

BMD

Bone mineral density

BMP

Bone morphogenetic protein

CVA

Canonical variates analysis/discriminant analysis

LRP5

Low density lipoprotein receptor-related protein 5

PBS

Phosphate buffered saline

PCA

Principal components analysis

PNP

Non-osteoporotic patients

PP

Patients affected with age-related osteoporosis

RQ

Relative quantity

SD

Standard deviation

TGFB

Transforming growth factor beta

Wnt

Wingless

Notes

Acknowledgments

Thanks are due to Sankar Adhya (NIH, NCI, USA) for valuable advice and discussions. This work was supported by grants OTKA T032205 to L.O., OTKA NI 68218 to J.P.; OM 0028/2001 to L.O. and P.L., OM 0320/2004 to L.O., NKFP 1A/007/2004 to L.O., P.L. and T.V.; 454/2003 from the Ministry of Health, Social and Family Affairs to L.O., OTKA PD75496 to S.S., and by the János Bolyai fellowship of the HAS to S·S.

Supplementary material

438_2008_413_MOESM1_ESM.pdf (892 kb)
Supplementary Figures S1, S5; Supplementary Tables S2, S3, S4, S6, S7 (PDF 892 kb)

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Copyright information

© Springer-Verlag 2008

Authors and Affiliations

  • Adrienn Borsy
    • 1
    • 2
    • 4
  • János Podani
    • 3
    • 4
  • Viktor Stéger
    • 1
    • 2
  • Bernadett Balla
    • 5
  • Arnold Horváth
    • 4
  • János P. Kósa
    • 5
  • István GyurjánJr
    • 1
  • Andrea Molnár
    • 1
  • Zoltán Szabolcsi
    • 1
    • 2
  • László Szabó
    • 2
  • Eéna Jakó
    • 4
  • Zoltán Zomborszky
    • 6
  • János Nagy
    • 7
  • Szabolcs Semsey
    • 1
  • Tibor Vellai
    • 1
  • Péter Lakatos
    • 5
  • László Orosz
    • 1
    • 2
  1. 1.Department of GeneticsEötvös Loránd UniversityBudapestHungary
  2. 2.Institute of GeneticsAgricultural Biotechnology CenterGödöllőHungary
  3. 3.Department of Plant Taxonomy and EcologyEötvös Loránd UniversityBudapestHungary
  4. 4.Eötvös Loránd University eScience Regional Knowledge CentreEötvös Loránd UniversityBudapestHungary
  5. 5.1st Department of Internal MedicineSemmelweis UniversityBudapestHungary
  6. 6.Department of Fish and Pet Animal Breeding, Faculty of Animal ScienceUniversity of KaposvárKaposvárHungary
  7. 7.Deer Farm of the Pannonian Equestrian AcademyUniversity of KaposvárKaposvárHungary

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