Herniated intervertebral disk induces hypertrophy and ossification of ligamentum flavum

Young Mi Kang, Kyung Soo Suk, Byung Ho Lee, Hak Sun Kim, Kwang Il Lee, Si Young Park, Hwan Mo Lee, Seong Hwan Moon

Research output: Contribution to journalArticlepeer-review

21 Citations (Scopus)


Study Design: In vitro experiment using degenerated human ligamentum flavum (LF) and herniated intervertebral disk (IVD).

Objectives: To investigate the role and effect of degenerated and herniated IVDs on LF hypertrophy and ossification.

Summary of Background Data: Spinal stenosis is caused, in part, by hypertrophy and ossification of the LF, which are induced by aging and degenerative process. It is well known that degenerated IVDs spontaneously produce inflammatory cytokines. Therefore, we hypothesized that degenerated IVD may affect adjacent LF through secreted inflammatory cytokines.

Conclusions: Degenerated and herniated IVDs provide an important pathomechanism in hypertrophy and ossification of the LF through inflammatory cytokines.

Methods: LF and herniated lumbar IVD tissues were obtained during surgical spinal procedures. LF fibroblasts were isolated by enzymatic digestion of LF tissue. LF cell cultures were treated with disk supernatant from herniated IVDs. Secreted cytokines from IVD tissue culture were detected by enzymelinked immunosorbent assay. After analysis of cytotoxicity, DNA synthesis was measured. Reverse transcription-polymerase chain reaction for mRNA expressions of types I, II, III, V, and XI collagen and osteocalcin, and histochemical stains were performed.

Results: Supernatant from tissue culture of herniated IVD showed increased production of interleukin-1a, interleukin-6, tumor necrosis factor-α, prostaglandin E2, and nitric oxide compared with disk tissue culture from traumatic condition. There was no cytotoxicity in LF cells treated with disk supernatant from herniated IVDs. There was significant increase in DNA synthesis, upregulation in mRNA expression of types III, XI collagen and osteocalcin, whereas variable expression pattern of type I and V, and strong positive stains for Von Kossa and alkaline phosphatase in LF cultures with disk supernatant.

Original languageEnglish
Pages (from-to)382-389
Number of pages8
JournalJournal of Spinal Disorders and Techniques
Issue number7
Publication statusPublished - 2014 Oct 8
Externally publishedYes

Bibliographical note

Publisher Copyright:
Copyright © 2012 by Lippincott Williams & Wilkins.


  • Degeneration
  • Hypertrophy
  • Intervertebral disk
  • Ligamentum flavum
  • Ossification

ASJC Scopus subject areas

  • Surgery
  • Orthopedics and Sports Medicine
  • Clinical Neurology


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