Support of concept that migrating progenitor cells from stem cell niches contribute to normal regeneration of the adult mammal intervertebral disc: a descriptive study in the New Zealand white rabbit

Spine (Phila Pa 1976). 2012 Apr 20;37(9):722-32. doi: 10.1097/BRS.0b013e318231c2f7.


Study design: Descriptive experimental study performed in rabbits of 2 age groups.

Objective: To study and investigate presence of prechondrocytic cells and cell migration routes (MR) in the intervertebral disc (IVD) region to gain knowledge about the normal IVD regeneration pattern.

Summary of background data: Disc degeneration is thought to play a major role in patients with chronic lumbar pain. Regeneration processes and cell migration within the IVD have been sparsely described. Therefore, it is of interest to increase knowledge of these processes in order to understand pathological conditions of the IVD.

Methods: At the beginning of the experiment, 5-bromo-2-deoxyuridine (BrdU) in vivo labeling was performed in 2 groups of rabbits, 3 and 9 months old (total 27 rabbits). BrdU is incorporated into DNA during mitosis, and then it is gradually diluted with each cell division until it finally disappears. Incorporation of BrdU was then visualized by immunohistochemistry (IHC) at different time points providing cell division pattern and presence of slow-cycling cells in the IVD region. IVD tissue was investigated by IHC for growth and differentiation factor-5 (GDF5), SOX9 (chondrogenic lineage markers), SNAIL homolog 1 (SNAI1), SNAIL homolog 2 (SLUG) (migration markers), and β1-INTEGRIN (cellular adhesion marker). In addition, GDF5, SOX9, and BMPRIB expression were investigated on genetic level.

Results: BrdU cells were observed in early time points in the IVD niche, adjacent to the epiphyseal plate, at later time points mainly in outer region of the annulus fibrosus for both age groups of rabbits, indicating a gradual migration of cells. The presence of SLUG, SNAI1, GDF5, SOX9, and β1-INTEGRIN was found in same regions.

Conclusion: The results suggest a cellular MR from the IVD stem cell niche toward the annulus fibrosus and the inner parts of the IVD. These findings may be of importance for understanding IVD regenerative mechanisms and for future development of biological treatment strategies.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Age Factors
  • Aging / genetics
  • Aging / metabolism
  • Aging / physiology*
  • Animals
  • Biomarkers / metabolism
  • Bone Morphogenetic Protein Receptors, Type I / genetics
  • Bone Morphogenetic Protein Receptors, Type I / metabolism
  • Cell Differentiation
  • Cell Lineage
  • Cell Movement*
  • Cell Proliferation
  • Chondrogenesis
  • DNA Replication
  • Female
  • Gene Expression Regulation
  • Growth Differentiation Factor 5 / genetics
  • Growth Differentiation Factor 5 / metabolism
  • Immunohistochemistry
  • Integrin beta1 / metabolism
  • Intervertebral Disc / growth & development*
  • Intervertebral Disc / metabolism
  • Rabbits
  • Regeneration*
  • SOX9 Transcription Factor / genetics
  • SOX9 Transcription Factor / metabolism
  • Snail Family Transcription Factors
  • Stem Cell Niche*
  • Stem Cells / metabolism
  • Stem Cells / physiology*
  • Transcription Factors / metabolism


  • Biomarkers
  • Growth Differentiation Factor 5
  • Integrin beta1
  • SOX9 Transcription Factor
  • Snail Family Transcription Factors
  • Transcription Factors
  • Bone Morphogenetic Protein Receptors, Type I