Skip to main content

Advertisement

SpringerLink
Log in

Microarray expression profiling identifies genes with altered expression in Adolescent Idiopathic Scoliosis

  • Original Article
  • Published:
European Spine Journal Aims and scope Submit manuscript

Abstract

Purpose

Adolescent Idiopathic Scoliosis (AIS) is considered a complex genetic disease, in which malfunctioning or dysregulation of one or more genes has been proposed to be responsible for the expressed phenotype. However, to date, no disease causing genes has been identified and the pathogenesis of AIS remains unknown. The aim of this study is, therefore, to identify specific molecules with differing expression patterns in AIS compared to healthy individuals.

Methods

Microarray analysis and quantitative RT-PCR have examined differences in the gene transcription profile between primary osteoblasts derived from spinal vertebrae of AIS patients and those of healthy individuals.

Results

There are 145 genes differentially expressed in AIS osteoblasts. A drastic and significant change has been noted particularly in the expression levels of Homeobox genes (HOXB8, HOXB7, HOXA13, HOXA10), ZIC2, FAM101A, COMP and PITX1 in AIS compared to controls. Clustering analysis revealed the interaction of these genes in biological pathways crucial for bone development, in particular in the differentiation of skeletal elements and structural integrity of the vertebrae.

Conclusions

This study reports on the expression of molecules that have not been described previously in AIS. We also provide for the first time gene interaction pathways in AIS pathogenesis. These genes are involved in various bone regulatory and developmental pathways and many of them can be grouped into clusters to participate in a particular biological pathway. Further studies can be built on our findings to further elucidate the association between different biological pathways and the pathogenesis of AIS.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Je L (1995) Idiopathic Scoliosis. In: Winter RB, Ogilive JW (eds) Lonstein JE BD. Moe’s textbook of scoliosis and other spinal deformaties. WB Saunders, Philadelphia, pp 219–256

    Google Scholar 

  2. Cavallaro Goodman C, Fuller KS (2009) Pathology: implications for the physical therapist. Saunders. WB/CO, St. Louis

    Google Scholar 

  3. Winter RB (1979) Posterior spinal fusion in scoliosis: indications technique and results. Orthop Clin N Am 10:787–800

    CAS  Google Scholar 

  4. Dubousset JQP, Thillard M (1983) Experimental scoliosis induced by pineal and diencephalic lesions in young chickens: its relation with clinical findings. Orthop Trans 7:7–12

    Google Scholar 

  5. Machida M, Dubousset J, Imamura Y, Miyashita Y, Yamada T, Kimura J (1996) Melatonin a possible role in pathogenesis of adolescent idiopathic scoliosis. Spine 21:1147–1152

    Article  PubMed  CAS  Google Scholar 

  6. Taylor TK, Ghosh P, Bushell GR (1981) The contribution of the intervertebral disk to the scoliotic deformity. Clin Orthop Relat Res 156:79–90

    PubMed  Google Scholar 

  7. Sahlstrand T, Petruson B (1979) A study of labyrinthine function in patients with adolescent idiopathic scoliosis I. An electro-nystagmographic study. Acta orthop Scand 50:759–769

    Article  PubMed  CAS  Google Scholar 

  8. Kindsfater K, Lowe T, Lawellin D, Weinstein D, Akmakjian J (1994) Levels of platelet calmodulin for the prediction of progression and severity of adolescent idiopathic scoliosis. J Bone Jt Surg Am 76:1186–1192

    CAS  Google Scholar 

  9. Nissinen M, Heliovaara M, Seitsamo J, Poussa M (1993) Trunk asymmetry. posture. growth. and risk of scoliosis. A three-year follow-up of Finnish prepubertal school children. Spine 18:8–13

    Article  PubMed  CAS  Google Scholar 

  10. Wise CA, Barnes R, Gillum J, Herring JA, Bowcock AM, Lovett M (2000) Localization of susceptibility to familial idiopathic scoliosis. Spine 25:2372–2380

    Article  PubMed  CAS  Google Scholar 

  11. Edery P, Margaritte-Jeannin P, Biot B, Labalme A, Bernard JC, Chastang J, Kassai B, Plais MH, Moldovan F, Clerget-Darpoux F (2011) New disease gene location and high genetic heterogeneity in idiopathic scoliosis. Eur J Hum Genet 19:865–869. doi:10.1038/ejhg.2011.31

    Article  PubMed  CAS  Google Scholar 

  12. Sharma S, Gao X, Londono D, Devroy SE, Mauldin KN, Frankel JT, Brandon JM, Zhang D, Li QZ, Dobbs MB, Gurnett CA, Grant SF, Hakonarson H, Dormans JP, Herring JA, Gordon D, Wise CA (2011) Genome-wide association studies of adolescent idiopathic scoliosis suggest candidate susceptibility genes. Hum Mol Genet 20:1456–1466. doi:10.1093/hmg/ddq571

    Article  PubMed  CAS  Google Scholar 

  13. Letellier K, Azeddine B, Parent S, Labelle H, Rompre PH, Moreau A, Moldovan F (2008) Estrogen cross-talk with the melatonin signaling pathway in human osteoblasts derived from adolescent idiopathic scoliosis patients. J Pineal Res 45:383–393. doi:10.1111/j.1600-079X.2008.00603.x

    Article  PubMed  CAS  Google Scholar 

  14. Chan V, Fong GC, Luk KD, Yip B, Lee MK, Wong MS, Lu DD, Chan TK (2002) A genetic locus for adolescent idiopathic scoliosis linked to chromosome 19p13.3. Am J Hum Genet 71:401–406. doi:10.1086/341607

    Article  PubMed  CAS  Google Scholar 

  15. Montanaro L, Parisini P, Greggi T, Di Silvestre M, Campoccia D, Rizzi S, Arciola CR (2006) Evidence of a linkage between matrilin-1 gene (MATN1) and idiopathic scoliosis. Scoliosis 1:21. doi:10.1186/1748-7161-1-21

    Article  PubMed  Google Scholar 

  16. Ocaka L, Zhao C, Reed JA, Ebenezer ND, Brice G, Morley T, Mehta M, O’Dowd J, Weber JL, Hardcastle AJ, Child AH (2008) Assignment of two loci for autosomal dominant adolescent idiopathic scoliosis to chromosomes 9q31.2-q34.2 and 17q25.3-qtel. J Med Genet 45:87–92. doi:10.1136/jmg.2007.051896

    Article  PubMed  CAS  Google Scholar 

  17. McNulty CL, Peres JN, Bardine N, van den Akker WM, Durston AJ (2005) Knockdown of the complete Hox paralogous group 1 leads to dramatic hindbrain and neural crest defects. Development 132:2861–2871. doi:10.1242/dev.01872

    Article  PubMed  CAS  Google Scholar 

  18. Pollock RA, Sreenath T, Ngo L, Bieberich CJ (1995) Gain of function mutations for paralogous Hox genes: implications for the evolution of Hox gene function. Proc Natl Acad Sci USA 92:4492–4496

    Article  PubMed  CAS  Google Scholar 

  19. Yang X, Ji X, Shi X, Cao X (2000) Smad1 domains interacting with Hoxc-8 induce osteoblast differentiation. J Biol Chem 275:1065–1072

    Article  PubMed  CAS  Google Scholar 

  20. Riggs BL, Khosla S, Melton LJ 3rd (2002) Sex steroids and the construction and conservation of the adult skeleton. Endocr Rev 23:279–302

    Article  PubMed  CAS  Google Scholar 

  21. Mortlock DP, Innis JW (1997) Mutation of HOXA13 in hand-foot-genital syndrome. Nat Genet 15:179–180. doi:10.1038/ng0297-179

    Article  PubMed  CAS  Google Scholar 

  22. Logan M, Tabin CJ (1999) Role of Pitx1 upstream of Tbx4 in specification of hindlimb identity. Science 283:1736–1739

    Article  PubMed  CAS  Google Scholar 

  23. Gurnett CA, Alaee F, Kruse LM, Desruisseau DM, Hecht JT, Wise CA, Bowcock AM, Dobbs MB (2008) Asymmetric lower-limb malformations in individuals with homeobox PITX1 gene mutation. Am J Hum Genet 83:616–622. doi:10.1016/j.ajhg.2008.10.004

    Article  PubMed  CAS  Google Scholar 

  24. Briggs MD, Chapman KL (2002) Pseudoachondroplasia and multiple epiphyseal dysplasia.: mutation review molecular interactions, and genotype to phenotype correlations. Hum Mutat 19:465–478. doi:10.1002/humu.10066

    Article  PubMed  CAS  Google Scholar 

  25. Fendri K, Moldovan F (2011) Potential role of COMP as a biomarker for adolescent idiopathic scoliosis. Med Hypotheses 76:762–763. doi:10.1016/j.mehy.2011.01.038

    Article  PubMed  CAS  Google Scholar 

  26. Tsui FW, Haroon N, Reveille JD, Rahman P, Chiu B, Tsui HW, Inman RD (2010) Association of an ERAP1 ERAP2 haplotype with familial ankylosing spondylitis. Ann Rheum Dis 69:733–736. doi:10.1136/ard.2008.103804

    Article  PubMed  CAS  Google Scholar 

  27. Hamilton JP (2011) Epigenetics: principles and practice. Dig Dis 29:130–135. doi:10.1159/000323874

    Article  PubMed  Google Scholar 

  28. Silahtaroglu A, Stenvang J (2010) MicroRNAs epigenetics and disease. Essays Biochem 48:165–185. doi:10.1042/bse0480165

    Article  PubMed  CAS  Google Scholar 

  29. Burwell RG, Dangerfield PH, Moulton A, Grivas TB (2011) Adolescent idiopathic scoliosis (AIS), environment. exposome and epigenetics: a molecular perspective of postnatal normal spinal growth and the etiopathogenesis of AIS with consideration of a network approach and possible implications for medical therapy. Scoliosis 6:26. doi:10.1186/1748-7161-6-26

    Article  PubMed  Google Scholar 

  30. Qiu XS, Tang NL, Yeung HY, Lee KM, Hung VW, Ng BK, Ma SL, Kwok RH, Qin L, Qiu Y, Cheng JC (2007) Melatonin receptor 1B (MTNR1B) gene polymorphism is associated with the occurrence of adolescent idiopathic scoliosis. Spine (Phila Pa 1976) 32(16):1748–1753

    Google Scholar 

  31. Wu J, Qiu Y, Zhang L, Sun Q, Qiu X, He Y (2006) Association of estrogen receptor gene polymorphisms with susceptibility to adolescent idiopathic scoliosis. Spine (Phila Pa 1976) 31(10):1131–1136

    Google Scholar 

  32. Alden KJ, Marosy B, Nzegwu N, Justice CM, Wilson AF, Miller NH (2006) Idiopathic scoliosis: identification of candidate regions on chromosome 19p13. Spine (Phila Pa 1976) 31(16):1815–1819

    Google Scholar 

  33. Raggio CL, Giampietro PF, Dobrin S, Zhao C, Dorshorst D, Ghebranious N, Weber JL, Blank RD (2009) A novel locus for adolescent idiopathic scoliosis on chromosome 12p. J Orthop Res 27:1366–1372

    Google Scholar 

  34. Justice CM, Miller NH, Marosy B, Zhang J, Wilson AF (2003) Familial idiopathic scoliosis: evidence of an X-linked susceptibility locus. Spine 28:589–594

    Google Scholar 

  35. Salehi LB, Mangino M, De Serio S, De Cicco D, Capon F, Semprini S, Pizzuti A, Novelli G, Dallapiccola B (2002) Assignment of a locus for autosomal dominant idiopathic scoliosis (IS) to human chromosome 17p11. Hum Genet 111:401–404

    Google Scholar 

Download references

Acknowledgments

FM and PE were supported by Yves Cotrel Foundation and SAP was supported by CHU Sainte-Justine and Foundation of the Stars scholarship.

Conflict of interest

None.

Author information

Authors and Affiliations

  1. Sainte-Justine Hospital Research Center, 3175, Chemin de la Cote Ste-Catherine, Montreal, Quebec, H3T 1C5, Canada

    Khaled Fendri, Shunmoogum A. Patten, Gabriel N. Kaufman, Charlotte Zaouter, Stefan Parent, Guy Grimard & Florina Moldovan

  2. Faculty of Dentistry, University of Montreal, C.P. 6128, succursale Centre-ville, Montréal, Québec, H3C 3J7, Canada

    Shunmoogum A. Patten & Florina Moldovan

  3. Cytogenetics Service, Civil Hospice of Lyon, Lyon, France

    Patrick Edery

Authors
  1. Khaled Fendri
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Shunmoogum A. Patten
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Gabriel N. Kaufman
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Charlotte Zaouter
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Stefan Parent
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Guy Grimard
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Patrick Edery
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Florina Moldovan
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Florina Moldovan.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Fendri, K., Patten, S.A., Kaufman, G.N. et al. Microarray expression profiling identifies genes with altered expression in Adolescent Idiopathic Scoliosis. Eur Spine J 22, 1300–1311 (2013). https://doi.org/10.1007/s00586-013-2728-2

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00586-013-2728-2

Keywords

Search

Navigation