SpringerLink
Log in

Hypertrophy of the ligamentum flavum in lumbar spinal canal stenosis is associated with increased bFGF expression

  • Original Article
  • Published:
International Orthopaedics Aims and scope Submit manuscript

Abstract

Purpose

A prospective study was undertaken to investigate basic fibroblast growth factor (bFGF) expression in hypertrophic ligamentum flavum (LF) from patients with lumbar spinal canal stenosis (LSCS) and to determine whether there was a correlation of bFGF expression with LF thickness.

Methods

Twenty patients with lumbar spinal canal stenosis were enrolled in this study. bFGF mRNA and protein expressions in LF were analyzed using quantitative reverse transcriptase-polymerase chain reaction (RT-PCR), immunohistochemistry, and enzyme-linked immunosorbent assay (ELISA), respectively. The thickness of LF was measured by axial T1-weighted magnetic resonance imaging.

Results

Expression of bFGF was substantially higher in the hypertrophic LF group than in the control group (P < 0.001) as quantified by quantitative real-time PCR. In immunohistochemical study, bFGF was positively stained on the fibroblasts within hypertrophic LF compared to nonpathologic LF of controls. Subsequent ELISA analysis revealed that bFGF concentration in the hypertrophic LF group was remarkably higher than that in the control group (P = 0.003). The thickness of LF in the hypertrophic LF was significantly greater than that in the control group (P < 0.001). LSCS patients with greater severity of LF hypertrophy had significantly higher bFGF levels in the LF tissues (P < 0.001). Furthermore, the bFGF concentration exhibited a positive correlation with the LF thickness (r = 0.974, P < 0.001).

Conclusions

These findings suggest that the increased expression of bFGF is associated with the hypertrophy of ligamentum flavum in patients with LSCS.

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

Access this article

Log in via an institution

Subscribe and save

Springer+ Basic
EUR 32.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or Ebook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

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

Similar content being viewed by others

References

  1. Szpalski M, Gunzburg R (2003) Lumbar spinal stenosis in the elderly: an overview. Eur Spine J 12:S170–S175

    Article  PubMed  Google Scholar 

  2. Hansson T, Suzuki N, Hebelka H, Gaulitz A (2009) The narrowing of the lumbar spinal canal during loaded MRI: the effects of the disc and ligamentum flavum. Eur Spine J 18:679–686

    Article  PubMed  Google Scholar 

  3. Saint-Louis LA (2001) Lumbar spinal stenosis assessment with computed tomography, magnetic resonance imaging, and myelography. Clin Orthop Relat Res 384:122–136

    Article  PubMed  Google Scholar 

  4. Alzheimer C, Werner S (2002) Fibroblast growth factors and neuroprotection. Adv Exp Med Biol 513:335–351

    Article  PubMed  CAS  Google Scholar 

  5. Thomas KA (1987) Fibroblast growth factors. FASEB J 1:434–440

    PubMed  CAS  Google Scholar 

  6. Honsawek S, Yuktanandana P, Tanavalee A, Saetan N, Anomasiri W, Parkpian V (2012) Correlation between plasma and synovial fluid basic fibroblast growth factor with radiographic severity in primary knee osteoarthritis. Int Orthop 36:981–985

    Article  PubMed  Google Scholar 

  7. Barrientos S, Stojadinovic O, Golinko MS, Brem H, Tomic-Canic M (2008) Growth factors and cytokines in wound healing. Wound Repair Regen 16:585–601

    Article  PubMed  Google Scholar 

  8. Przybylski M (2009) A review of the current research on the role of bFGF and VEGF in angiogenesis. J Wound Care 18:516–519

    PubMed  CAS  Google Scholar 

  9. Yayama T, Baba H, Furusawa N, Kobayashi S, Uchida K, Kokubo Y, Noriki S, Imamura Y, Fukuda M (2005) Pathogenesis of calcium crystal deposition in the ligamentum flavum correlates with lumbar spinal canal stenosis. Clin Exp Rheumatol 23:637–643

    PubMed  CAS  Google Scholar 

  10. Livak KJ, Schmittgen TD (2001) Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods 25:402–408

    Article  PubMed  CAS  Google Scholar 

  11. Fukuyama S, Nakamura T, Ikeda T, Takagi K (1995) The effect of mechanical stress on hypertrophy of the lumbar ligamentum flavum. J Spinal Disord 8:126–130

    Article  PubMed  CAS  Google Scholar 

  12. Park JB, Chang H, Lee JK (2001) Quantitative analysis of transforming growth factor-beta 1 in ligamentum flavum of lumbar spinal stenosis and disc herniation. Spine (Phila Pa 1976) 26:E492–E495

    Article  CAS  Google Scholar 

  13. Giles LG, Kaveri MJ (1990) Some osseous and soft tissue causes of human intervertebral canal (foramen) stenosis. J Rheumatol 17:1474–1481

    PubMed  CAS  Google Scholar 

  14. Binder DK, Schmidt MH, Weinstein PR (2002) Lumbar spinal stenosis. Semin Neurol 22:157–166

    Article  PubMed  Google Scholar 

  15. Schrader P, Grob D, Rahn BA, Cordey J, Dvorak J (1999) Histology of the ligamentum flavum in patients with degenerative lumbar spinal stenosis. Eur Spine J 8:323–328

    Article  PubMed  CAS  Google Scholar 

  16. Yahia LH, Garzon S, Strykowski H, Rivard CH (1990) Ultrastructure of the human interspinous ligament and ligamentum flavum. A preliminary study. Spine 15:262–268

    Article  PubMed  CAS  Google Scholar 

  17. Yoshida M, Shima K, Tangiguti Y, Tamaki T, Tanaka T (1992) Hypertrophied ligamentum flavum in lumbar spinal canal stenosis. Pathogenesis and morphologic and immunohistochemical observation. Spine 17:1353–1360

    Article  PubMed  CAS  Google Scholar 

  18. Löhr M, Hampl JA, Lee JY, Ernestus RI, Deckert M, Stenzel W (2011) Hypertrophy of the lumbar ligamentum flavum is associated with inflammation-related TGF-β expression. Acta Neurochir (Wien) 153:134–141

    Article  Google Scholar 

  19. Zhang Y, Chen J, Zhong ZM, Yang D, Zhu Q (2010) Is platelet-derived growth factor-BB expression proportional to fibrosis in the hypertrophied lumber ligamentum flavum? Spine (Phila Pa 1976) 35:E1479–E1486

    Article  Google Scholar 

  20. Zhong ZM, Zha DS, **ao WD, Wu SH, Wu Q, Zhang Y, Liu FQ, Chen JT (2011) Hypertrophy of ligamentum flavum in lumbar spine stenosis associated with the increased expression of connective tissue growth factor. J Orthop Res 29:1592–1597

    Article  PubMed  CAS  Google Scholar 

  21. Morita H, Shinzato T, David G, Mizutani A, Habuchi H, Fujita Y, Ito M, Asai J, Maeda K, Kimata K (1994) Basic fibroblast growth factor-binding domain of heparan sulfate in the human glomerulosclerosis and renal tubulointerstitial fibrosis. Lab Invest 71:528–535

    PubMed  CAS  Google Scholar 

  22. Inoue Y, King TE Jr, Barker E, Daniloff E, Newman LS (2002) Basic fibroblast growth factor and its receptors in idiopathic pulmonary fibrosis and lymphangioleiomyomatosis. Am J Respir Crit Care Med 166:765–773

    Article  PubMed  Google Scholar 

  23. Peng X, Wang B, Wang T, Zhao Q (2005) Expression of basic fibroblast growth factor in rat liver fibrosis and hepatic stellate cells. J Huazhong Univ Sci Technolog Med Sci 25:166–169

    Article  PubMed  CAS  Google Scholar 

  24. Poonpukdee J, Chalermpanpipat C, Payungporn S, Honsawek S (2012) Basic fibroblast growth factor expression in hypertrophic ligamentum flavum of lumbar spinal stenosis. Asian Biomed 6:99–104

    Google Scholar 

Download references

Acknowledgments

This investigation was supported by Ratchadapiseksompotch Fund, Faculty of Medicine, Chulalongkorn University, Thailand Research Fund, and National Research Council of Thailand. We are grateful to Mr. Preecha Ruangvejvorachai for kindly technical assistance and Chulalongkorn Medical Research Center (ChulaMRC) for generously providing facilities.

Author information

Authors and Affiliations

  1. Department of Orthopaedics, Faculty of Medicine, Chulalongkorn University, King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Rama IV road, Patumwan, Bangkok, 10330, Thailand

    Sittisak Honsawek, Chookiet Chalermpanpipat, Worawat Limthongkul, Wicharn Yingsakmongkol & Vinai Parkpian

  2. Department of Biochemistry, Faculty of Medicine, Chulalongkorn University, Bangkok, 10330, Thailand

    Sittisak Honsawek, Jariya Poonpukdee & Sunchai Payungporn

  3. Department of Anatomy, Faculty of Medicine, Chulalongkorn University, Bangkok, 10330, Thailand

    Chookiet Chalermpanpipat

  4. Department of Pathology, Faculty of Medicine, Chulalongkorn University, Bangkok, 10330, Thailand

    Voranuch Thanakit

Authors
  1. Sittisak Honsawek
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jariya Poonpukdee
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Chookiet Chalermpanpipat
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Sunchai Payungporn
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Worawat Limthongkul
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Wicharn Yingsakmongkol
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Voranuch Thanakit
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Vinai Parkpian
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Sittisak Honsawek.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Honsawek, S., Poonpukdee, J., Chalermpanpipat, C. et al. Hypertrophy of the ligamentum flavum in lumbar spinal canal stenosis is associated with increased bFGF expression. International Orthopaedics (SICOT) 37, 1387–1392 (2013). https://doi.org/10.1007/s00264-013-1864-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00264-013-1864-y

Keywords

Search

Navigation