Skip to main content
SpringerLink
Log in

The effect of calmodulin antagonists on scoliosis: bipedal C57BL/6 mice model

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

Abstract

C57BL6 mice are melatonin deficient from birth and have been shown to develop scoliosis when rendered bipedal. Our previous work suggested that tamoxifen and trifluoperozine may change the natural course of scoliosis in a chicken model. The objective of this study was to analyze whether the incidence of scoliosis or the magnitude of curves may be decreased by the administration of pharmacological agents tamoxifen or trifluoperozine in a mice scoliosis model. Sixty female 3-week-old C57BL6 mice underwent amputations of forelimbs and tails. Available 57 mice were divided into three groups, Group-I received no medications whereas Groups II and III received 10 mg TMX and 10 mg TMX + 10 mg TFP per liter of daily water supply, respectively. PA scoliosis X-rays were obtained at 20th and 40th weeks. Deformities were compared for incidence and the severity of the curves as well as disease progression or regression. At 20th week, overall, upper thoracic (UT), lower thoracic (T), and lumbar (L) scoliosis rates were similar (P = 0.531; P = 0.209; P = 0.926; P = 0.215, respectively) but thoraco-lumbar (TL) scoliosis rate was higher inTMX group (P = 0.036). However, at 40th week, although TL and L rates were similar (P = 0.628, P = 0.080), overall rate as well as the rates of UT and T scoliosis of TMX group were significantly lower (P = 0.001, P = 0.011, P = 0.001, respectively). As for curve magnitudes, T mean Cobb angle at 20th week was significantly higher in the C group (14 ± 2.55) compared to TMX + TFP group (9 ± 2.708; P = 0.033); at 40th week, TL mean Cobb angle was lower in the TMX + TFP group (17.50 ± 3.45) compared to C (29.40 ± 5.98; P = 0.031); and TMX group had lower TL Cobb angles compared to C (8.67 ± 11.72) although not significant (P = 0.109). Double curve incidence at 40th week was significantly lower in TMX group compared to other groups (P = 0.001), triple curve incidence was lower in TMX + TFP and TMX groups, albeit not significant (P = 0.167). Between the 20th and 40th weeks, overall, double curve, and UT scoliosis rates showed an increase in C and TMX + TFP groups whereas TMX group showed a decline (P = 0.01, P = 0.002, P = 0.007, respectively). When specific regions were compared a similar significant difference was observed (P = 0.012 for upper thoracic; P = 0.018 for thoracic; P = 0.047 for thoraco-lumbar). This study has demonstrated that TMX is effective in changing the natural history of scoliotic deformities in C57BL6 mice model favorably.

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
Fig. 4
Fig. 5
Fig. 6
Fig. 7

Similar content being viewed by others

References

  1. Acaroglu RE, Akel I, Alanay A, Yazici M, Marcucio R (2009) Comparison of the melatonin and calmodulin in paravertebral muscle and platelets of patients with or without adolescent ıdiopathic scoliosis. Spine J (under review)

  2. Ahn UM, Ahn NU, Nallamshetty L et al (2002) The etiology of adolescent idiopathic scoliosis. Am J Orthop 31:387–395

    PubMed  Google Scholar 

  3. Akel I, Kocak O, Bozkurt G, Alanay A, Marcucio R, Acaroglu RE (2009) The effect of calmodulin antagonists on experimental scoliosis: a pinealectomized chicken model. Spine J (in press)

  4. Bagnall KM, Beuerlein M, Johnson P et al (2001) Pineal transplantation after pinealectomy in young chickens has no effect on the development of scoliosis. Spine 26:1022–1027. doi:10.1097/00007632-200105010-00007

    Article  PubMed  CAS  Google Scholar 

  5. Cheung WY (1980) Calmodulin plays a pivotal role in cellular regulation. Science 207:19–27. doi:10.1126/science.6243188

    Article  PubMed  CAS  Google Scholar 

  6. Dubousset JQPTM (1983) Experimental scoliosis induced by pineal and diencephalic lesions in young chickens: its relation with clinical findings. Orthop Trans 7:7

    Google Scholar 

  7. Gallo MA, Kaufman D (1997) Antagonistic and agonistic effects of tamoxifen: significance in human cancer. Semin Oncol 24(Suppl 1):S1-71–S1-80

    Google Scholar 

  8. Grivas TB, Savvidou OD (2007) Melatonin the “light of night” in human biology and adolescent idiopathic scoliosis. Scoliosis 2:6. doi:10.1186/1748-7161-2-6

    Article  PubMed  Google Scholar 

  9. Lowe TG, Edgar M, Margulies JY et al (2000) Etiology of idiopathic scoliosis: current trends in research. J Bone Joint Surg 82-A:1157–1168

    PubMed  CAS  Google Scholar 

  10. Machida M, Dubousset J, Imamura Y et al (1994) Pathogenesis of idiopathic scoliosis: SEPs in chicken with experimentally induced scoliosis and in patients with idiopathic scoliosis. J Pediatr Orthop 14:329–335

    PubMed  CAS  Google Scholar 

  11. Machida M, Dubousset J, Imamura Y et al (1995) Role of melatonin deficiency in the development of scoliosis in pinealectomized chickens. J Bone Joint Surg Br 77:134–138

    PubMed  CAS  Google Scholar 

  12. Machida M, Dubousset J, Imamura Y et al (1996) Melatonin. A possible role in pathogenesis of adolescent idiopathic scoliosis. Spine 21:1147–1152. doi:10.1097/00007632-199605150-00005

    Article  PubMed  CAS  Google Scholar 

  13. Machida M, Miyashita Y, Murai I et al (1997) Role of serotonin for scoliotic deformity in pinealectomized chicken. Spine 22:1297–1301. doi:10.1097/00007632-199706150-00004

    Article  PubMed  CAS  Google Scholar 

  14. Machida M, Murai I, Miyashita Y et al (1999) Pathogenesis of idiopathic scoliosis. Experimental study in rats. Spine 24:1985–1989. doi:10.1097/00007632-199910010-00004

    Article  PubMed  CAS  Google Scholar 

  15. Machida M (1999) Cause of idiopathic scoliosis. Spine 24:2576–2583. doi:10.1097/00007632-199912150-00004

    Article  PubMed  CAS  Google Scholar 

  16. Machida M, Dubousset J, Satoh T et al (2001) Pathologic mechanism of experimental scoliosis in pinealectomized chickens. Spine 26:E385–E391. doi:10.1097/00007632-200109010-00006

    Article  PubMed  CAS  Google Scholar 

  17. Machida M, Dubousset J, Yamada T et al (2006) Experimental scoliosis in melatonin-deficient C57BL/6J mice without pinealectomy. J Pineal Res 41(1):1–7

    Article  PubMed  CAS  Google Scholar 

  18. Miller NH (2002) Genetics of familial idiopathic scoliosis. Clin Orthop Relat Res 60–64. doi:10.1097/00003086-200208000-00009

  19. Pan G, Vickers SM, Pickens A et al (1999) Apoptosis and tumorigenesis in human cholangiocarcinoma cells ınvolvement of Fas/APO-1 (CD95) and calmodulin. Am J Pathol 155(1)

  20. Poon AMS, Cheung KMC et al (2006) Changes in melatonin receptors in relation to the development of scoliosis in pinealectomized chickens. Spine 18:2043–2047. doi:10.1097/01.brs.0000231796.49827.39

    Google Scholar 

  21. Porter RW (2001) The pathogenesis of idiopathic scoliosis: uncoupled neuro-osseous growth? Eur Spine J 10:473–481. doi:10.1007/s005860100311

    Article  PubMed  CAS  Google Scholar 

  22. Roach JW (1999) Adolescent idiopathic scoliosis. Orthop Clin North Am 30:353–365. doi:10.1016/S0030-5898(05)70092-4

    Article  PubMed  CAS  Google Scholar 

  23. Soto-Vega E, Meza I, Ramirez-Rodriguez G et al (2004) Melatonin stimulates calmodulin phosphorylation by protein kinase C. J Pineal Res 37:98–106. doi:10.1111/j.1600-079X.2004.00141.x

    Article  PubMed  CAS  Google Scholar 

  24. Turgut M, Yenisey C, Uysal A et al (2003) The effects of pineal gland transplantation on the production of spinal deformity and serum melatonin level following pinealectomy in the chicken. Eur Spine J

  25. Turhan E, Acaroglu E, Bozkurt G (2006) Unilateral enucleation affects the laterality but not the incidence of scoliosis in pinealectomized chicken. Spine 15:133–138

    Article  Google Scholar 

  26. Xia Z, Storm DR (1997) Calmodulin-regulated adenylyl cyclases and neuromodulation. Curr Opin Neurobiol 7:391–396. doi:10.1016/S0959-4388(97)80068-2

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

This project was supported by a research grant from the Scoliosis Research Society supplied by the “Fondation Cotrel”, Paris, France.

Author information

Authors and Affiliations

  1. Department of Orthopedics and Traumatology, Hacettepe University, 06100, Ankara, Turkey

    Ibrahim Akel, Gokhan Demirkıran, Ahmet Alanay & Emre Acaroglu

  2. Department of Biostatistics, Hacettepe University, Ankara, Turkey

    Sevilay Karahan

  3. Department of Orthopedic Surgery, University of California San Francisco, San Francisco, CA, USA

    Ralph Marcucio

Authors
  1. Ibrahim Akel
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Gokhan Demirkıran
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ahmet Alanay
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Sevilay Karahan
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Ralph Marcucio
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Emre Acaroglu
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Emre Acaroglu.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Akel, I., Demirkıran, G., Alanay, A. et al. The effect of calmodulin antagonists on scoliosis: bipedal C57BL/6 mice model. Eur Spine J 18, 499–505 (2009). https://doi.org/10.1007/s00586-009-0912-1

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00586-009-0912-1

Keywords

Search

Navigation