Skip to main content

Advertisement

SpringerLink
Log in

Evidence of Intrinsic Impairment of Osteoblast Phenotype at the Curve Apex in Girls With Adolescent Idiopathic Scoliosis

  • Published:
Spine Deformity Aims and scope Submit manuscript

Abstract

Study Design

An observational descriptive study based on a single cohort of patients.

Objective

To determine whether spinal facet osteoblasts at the curve apex display a different phenotype to osteoblasts from outside the curve in adolescent idiopathic scoliosis (AIS) patients.

Summary of Background Data

Intrinsic differences in the phenotype of spinal facet bone tissue and in spinal osteoblasts have been implicated in the pathology of AIS. However, no study has compared the phenotype of facet osteoblasts at the curve apex compared with outside the curve in AIS patients.

Methods

Facet spinal tissue was collected perioperatively from three sites, the concave and convex side at the curve apex and from outside the curve (noncurve) from three AIS female patients aged 13–16 years. Spinal tissue was analyzed by micro–computed tomography to determine bone mineral density (BMD) and trabecular structure. Primary osteoblasts were cultured from concave, convex, and noncurve facet bone chips. The phenotype of osteoblasts was determined by assessment of cellular proliferation, cellular metabolism (alkaline phosphatase and Seahorse Analyzer), bone nodule mineralization (Alizarin red assay), and the mRNA expression of Wnt signaling genes (quantitative reverse transcriptase polymerase chain reaction).

Results

Convex facet tissue exhibited greater BMD and trabecular thickness, compared with concave facet tissue. Osteoblasts at the convex side of the curve apex exhibited a significantly higher proliferative and metabolic phenotype and a greater capacity to form mineralized bone nodules, compared with concave osteoblasts. mRNA expression of SKP2 was significantly greater in both concave and convex osteoblasts, compared with noncurve osteoblasts. The expression of SFRP1 was significantly downregulated in convex osteoblasts, compared with either concave or noncurve.

Conclusions

Intrinsic differences that affect osteoblast function are exhibited by spinal facet osteoblasts at the curve apex in AIS patients.

Level of Evidence

Level IV, Prognostic.

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

Similar content being viewed by others

References

  1. Negrini S, De Mauroy JC, Grivas TB, et al. Actual evidence in the medical approach to adolescents with idiopathic scoliosis. Eur J Phys Rehabil Med 2014;50:87–92.

    CAS  PubMed  Google Scholar 

  2. Rainoldi L, Zaina F, Villafane JH, et al. Quality of life in normal and idiopathic scoliosis adolescents before diagnosis: reference values and discriminative validity of the SRS-22. A cross-sectional study of 1,205 pupils. Spine J 2015;15:662–7.

    Article  PubMed  Google Scholar 

  3. Zaina F, De Mauroy JC, Grivas T, et al. Bracing for scoliosis in 2014: state of the art. Eur J Phys Rehabil Med 2014;50:93–110.

    CAS  PubMed  Google Scholar 

  4. Cheung KM, Wang T, Qiu GX, et al. Recent advances in the aetiology of adolescent idiopathic scoliosis. Int Orthop 2008;32:729–34.

    Article  PubMed  Google Scholar 

  5. Dickson RA. The aetiology of spinal deformities. Lancet 1988;1:1151–5.

    Article  CAS  PubMed  Google Scholar 

  6. Newton Ede MM, Jones SW. Adolescent idiopathic scoliosis: evidence for intrinsic factors driving aetiology and progression. Int Orthop 2016;40:2075–80.

    Article  PubMed  Google Scholar 

  7. Cheng JC, Qin L, Cheung CS, et al. Generalized low areal and volumetric bone mineral density in adolescent idiopathic scoliosis. J Bone Miner Res 2000;15:1587–95.

    Article  CAS  PubMed  Google Scholar 

  8. Cheng JC, Tang SP, Guo X, et al. Osteopenia in adolescent idiopathic scoliosis: a histomorphometric study. Spine (Phila Pa 1976) 2001;26:E19–23.

    Article  Google Scholar 

  9. Suh KT, Lee SS, Hwang SH, et al. Elevated soluble receptor activator of nuclear factor-kappaB ligand and reduced bone mineral density in patients with adolescent idiopathic scoliosis. Eur Spine J 2007;16:1563–9.

    Article  PubMed  PubMed Central  Google Scholar 

  10. Cheng JC, Hung VW, Lee WT, et al. Persistent osteopenia in adolescent idiopathic scoliosis—longitudinal monitoring of bone mineral density until skeletal maturity. Stud Health Technol Inform 2006;123:47–51.

    CAS  PubMed  Google Scholar 

  11. Cheung CS, Lee WT, Tse YK, et al. Generalized osteopenia in adolescent idiopathic scoliosis—association with abnormal pubertal growth, bone turnover, and calcium intake? Spine (Phila Pa 1976) 2006;31:330–8.

    Article  Google Scholar 

  12. Lam TP, Hung VW, Yeung HY, et al. Abnormal bone quality in adolescent idiopathic scoliosis: a case-control study on 635 subjects and 269 normal controls with bone densitometry and quantitative ultrasound. Spine (Phila Pa 1976) 2011;36:1211–7.

    Article  Google Scholar 

  13. Eun IS, Park WW, Suh KT, et al. Association between osteoproteger-in gene polymorphism and bone mineral density in patients with adolescent idiopathic scoliosis. Eur Spine J 2009;18:1936–40.

    Article  PubMed  PubMed Central  Google Scholar 

  14. Man GC, Wang WW, Yeung BH, et al. Abnormal proliferation and differentiation of osteoblasts from girls with adolescent idiopathic scoliosis to melatonin. J Pineal Res 2010;49:69–77.

    CAS  PubMed  Google Scholar 

  15. Machida M, Dubousset J, Imamura Y, et al. Pathogenesis of idiopathic scoliosis: SEPs in chicken with experimentally induced scoliosis and in patients with idiopathic scoliosis. J Pediatr Orthop 1994;14:329–35.

    Article  CAS  PubMed  Google Scholar 

  16. Machida M, Dubousset J, Imamura Y, et al. Melatonin. A possible role in pathogenesis of adolescent idiopathic scoliosis. Spine (Phila Pa 1976) 1996;21:1147–52.

    Article  CAS  Google Scholar 

  17. Machida M, Dubousset J, Satoh T, et al. Pathologic mechanism of experimental scoliosis in pinealectomized chickens. Spine (Phila Pa 1976) 2001;26:E385–91.

    Article  Google Scholar 

  18. Machida M, Saito M, Dubousset J, et al. Pathological mechanism of idiopathic scoliosis: experimental scoliosis in pinealectomized rats. Eur Spine J 2005;14:843–8.

    Article  PubMed  Google Scholar 

  19. Bradford MM. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of proteindye binding. Anal Biochem 1976;72:248–54.

    Article  CAS  PubMed  Google Scholar 

  20. Gregory CA, Gunn WG, Peister A, et al. An Alizarin red-based assay of mineralization by adherent cells in culture: comparison with cetylpyridinium chloride extraction. Anal Biochem 2004;329:77–84.

    Article  CAS  PubMed  Google Scholar 

  21. Philp AM, Collier RL, Grover LM, et al. Resistin promotes the abnormal Type I collagen phenotype of subchondral bone in obese patients with end stage hip osteoarthritis. Sci Rep 2017;7:4042.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  22. Chang J, Jackson SG, Wardale J, et al. Hypoxia modulates the phenotype of osteoblasts isolated from knee osteoarthritis patients, leading to undermineralized bone nodule formation. Arthritis Rheumatol 2014;66:1789–99.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Brodner W, Krepler P, Nicolakis M, et al. Melatonin and adolescent idiopathic scoliosis. J Bone Joint Surg Br 2000;82:399–403.

    Article  CAS  PubMed  Google Scholar 

  24. Suh KT, Lee SS, Kim SJ, et al. Pineal gland metabolism in patients with adolescent idiopathic scoliosis. J Bone Joint Surg Br 2007;89:66–71.

    Article  CAS  PubMed  Google Scholar 

  25. Cheuk KY, Zhu TY, Yu FW, et al. Abnormal bone mechanical and structural properties in adolescent idiopathic scoliosis: a study with finite element analysis and Structural Model Index. Calcif Tissue Int 2015;97:343–52.

    Article  CAS  PubMed  Google Scholar 

  26. Li XF, Li H, Liu ZD, et al. Low bone mineral status in adolescent idiopathic scoliosis. Eur Spine J 2008;17:1431–40.

    Article  PubMed  PubMed Central  Google Scholar 

  27. Bovolenta P, Esteve P, Ruiz JM, et al. Beyond Wnt inhibition: new functions of secreted Frizzled-related proteins in development and disease. J Cell Sci 2008;121:737–46.

    Article  CAS  PubMed  Google Scholar 

  28. Uren A, Reichsman F, Anest V, et al. Secreted frizzled-related protein-1 binds directly to Wingless and is a biphasic modulator of Wnt signaling. J Biol Chem 2000;275:4374–82.

    Article  CAS  PubMed  Google Scholar 

  29. Bu XM, Zhao CH, Dai XW. Aberrant expression of Wnt antagonist SFRP1 in pancreatic cancer. Chin Med J (Engl) 2008;121:952–5.

    Article  CAS  Google Scholar 

  30. Chang L, Lei X, Qin YU, et al. Expression and prognostic value of SFRP1 and beta-catenin in patients with glioblastoma. Oncol Lett 2016;11:69–74.

    Article  CAS  PubMed  Google Scholar 

  31. Caldwell GM, Jones C, Gensberg K, et al. The Wnt antagonist sFRP1 in colorectal tumorigenesis. Cancer Res 2004;64:883–8.

    Article  CAS  PubMed  Google Scholar 

  32. Chen YZ, Liu D, Zhao YX, et al. Aberrant promoter methylation of the SFRPl gene may contribute to colorectal carcinogenesis: a metaanalysis. Tumour Biol 2014;35:9201–10.

    Article  CAS  PubMed  Google Scholar 

  33. Dees C, Schlottmann I, Funke R, et al. The Wnt antagonists DKK1 and SFRP1 are downregulated by promoter hypermethylation in systemic sclerosis. Ann Rheum Dis 2014;73:1232–9.

    Article  CAS  PubMed  Google Scholar 

  34. Svensson A, Norrby M, Libelius R, et al. Secreted frizzled related protein 1 (Sfrp1) and Wnt signaling in innervated and denervated skeletal muscle. J Mol Histol 2008;39:329–37.

    Article  CAS  PubMed  Google Scholar 

  35. Thacker G, Kumar Y, Khan MP, et al. Skp2 inhibits osteogenesis by promoting ubiquitin-proteasome degradation of Runx2. Biochim Biophys Acta 2016;1863:510–9.

    Article  CAS  PubMed  Google Scholar 

  36. Fujita T, Azuma Y, Fukuyama R, et al. Runx2 induces osteoblast and chondrocyte differentiation and enhances their migration by coupling with PI3K-Akt signaling. J Cell Biol 2004;166:85–95.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Thomas DM, Johnson SA, Sims NA, et al. Terminal osteoblast differentiation, mediated by runx2 and p27KIPl, is disrupted in osteosarcoma. J Cell Biol 2004;167:925–34.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Takarada T, Hinoi E, Nakazato R, et al. An analysis of skeletal development in osteoblast-specific and chondrocyte-specific runt-related transcription factor-2 (Runx2) knockout mice. J Bone Miner Res 2013;28:2064–9.

    Article  CAS  PubMed  Google Scholar 

  39. Komori T. Regulation of osteoblast differentiation by Runx2. Adv Exp Med Biol 2010;658:43–9.

    Article  CAS  PubMed  Google Scholar 

  40. Prince M, Banerjee C, Javed A, et al. Expression and regulation of Runx2/Cbfal and osteoblast phenotypic markers during the growth and differentiation of human osteoblasts. J Cell Biochem 2001;80:424–40.

    Article  CAS  PubMed  Google Scholar 

  41. Vimalraj S, Arumugam B, Miranda PJ, et al. Runx2: structure, function, and phosphorylation in osteoblast differentiation. Int J Biol Macromol 2015;78:202–8.

    Article  CAS  PubMed  Google Scholar 

  42. Hayes M, Gao X, Yu LX, et al. ptk7 mutant zebrafish models of congenital and idiopathic scoliosis implicate dysregulated Wnt signalling in disease. Nat Commun 2014;5:4777.

    Article  CAS  PubMed  Google Scholar 

  43. Andersen MR, Farooq M, Koefoed K, et al. Mutation of the planar cell polarity gene VANGL1 in adolescent idiopathic scoliosis. Spine (Phila Pa 1976) 2017;42:E702-7.

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Institute of Inflammation and Ageing, MRC-ARUK Centre for Musculoskeletal Ageing Research, School of Immunity, University of Birmingham, Birmingham, United Kingdom

    Mark J. Pearson PhD, Ashleigh M. Philp PhD, Hirah Haq, Megan E. Cooke BSc, Thomas Nicholson BSc & Simon W. Jones PhD

  2. School of Chemical Engineering, University of Birmingham, Birmingham, B15 2TT, United Kingdom

    Liam M. Grover PhD

  3. Royal Orthopaedic Hospital NHS Trust, Bristol Road South, Birmingham, United Kingdom

    Matthew Newton Ede MBBS

Authors
  1. Mark J. Pearson PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ashleigh M. Philp PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Hirah Haq
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Megan E. Cooke BSc
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Thomas Nicholson BSc
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Liam M. Grover PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Matthew Newton Ede MBBS
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Simon W. Jones PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Simon W. Jones PhD.

Additional information

Author disclosures: MJP (grants from Birmingham Orthopaedic Charity, during the conduct of the study), AMP (grants from Birmingham Orthopaedic Charity, during the conduct of the study), HH (none), MEC (none), TN (none), LMG (none), MNE (personal fees from Stryker and NuVasive; grants from British Scoliosis Research Foundation, United Kingdom, outside the submitted work), SWJ (grants from Birmingham Orthopaedic Charity, during the conduct of the study).

M.J. Pearson and A.M. Philp contributed equally to this work.

Funding: Birmingham Orthopaedic Charity.

Ethical approval: The study was approved by the Royal Orthopaedic Hospital Ethical Review panel (ROH16/002).

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Pearson, M.J., Philp, A.M., Haq, H. et al. Evidence of Intrinsic Impairment of Osteoblast Phenotype at the Curve Apex in Girls With Adolescent Idiopathic Scoliosis. Spine Deform 7, 533–542 (2019). https://doi.org/10.1016/j.jspd.2018.11.016

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1016/j.jspd.2018.11.016

Keywords

Search

Navigation