Comparative immunolocalisation of perlecan, heparan sulphate, fibroblast growth factor-18, and fibroblast growth factor receptor-3 and their prospective roles in chondrogenic and osteogenic development of the human foetal spine

Eur Spine J. 2013 Aug;22(8):1774-84. doi: 10.1007/s00586-013-2680-1. Epub 2013 Feb 10.

Abstract

Purpose: A comparative immunolocalisation study of perlecan, HS, FGF-18 and FGFR-3 in the 12-20-week gestational age human foetal spine was undertaken to identify spatiotemporal associations between these components to provide insights into prospective roles in spinal development.

Methods: Comparative immunolocalisations of matrix and cell associated components in Histochoice-fixed paraffin-embedded human foetal spinal tissues.

Results: The 12-14-week-old human foetal spine was a predominantly cartilaginous structure with the discs displaying a relative paucity of proteoglycan compared to the adjacent cartilaginous vertebral rudiments, notochordal remnants were also observed. HS and perlecan had a widespread distribution throughout the spine at 12 weeks, however, FGF-18 was only localised to the outer AF margins and hypertrophic cell condensations in the vertebral bodies. This contrasted with HS distributions at 14-20 weeks, which were prominent in the developing intervertebral disc (IVD). Ossification centres were also evident centrally within the vertebral rudiments surrounded by small columns of hypertrophic chondrocytes which expressed FGFR-3 and FGF-18 and upregulated levels of perlecan. FGF-18 also had a prominent localisation pattern in the developing IVD and the cartilaginous endplate while FGFR-3 was expressed throughout the disc interspace. This suggested roles for perlecan, FGF-18 and FGFR-3 in chondrogenic and osteogenic events which drive discal development and ossification of the vertebral bodies.

Conclusions: The above data supported a role for FGF-18 in discal development and in the terminal osteogenic differentiation of chondroprogenitor cell populations, which promote vertebral ossification during spinal development.

Publication types

  • Comparative Study

MeSH terms

  • Cartilage / cytology
  • Cartilage / embryology
  • Cartilage / metabolism
  • Cell Differentiation
  • Cell Proliferation
  • Chondrocytes / cytology
  • Chondrocytes / metabolism
  • Chondrogenesis / physiology*
  • Fetus / metabolism
  • Fibroblast Growth Factors / metabolism*
  • Heparan Sulfate Proteoglycans / metabolism*
  • Heparitin Sulfate / metabolism
  • Humans
  • Immunohistochemistry
  • Intervertebral Disc / cytology
  • Intervertebral Disc / embryology
  • Intervertebral Disc / metabolism
  • Notochord / cytology
  • Notochord / embryology
  • Notochord / metabolism
  • Osteogenesis / physiology*
  • Receptor, Fibroblast Growth Factor, Type 3 / metabolism*
  • Spine / embryology*
  • Spine / metabolism
  • Spine / physiopathology

Substances

  • Heparan Sulfate Proteoglycans
  • fibroblast growth factor 18
  • perlecan
  • Fibroblast Growth Factors
  • Heparitin Sulfate
  • FGFR3 protein, human
  • Receptor, Fibroblast Growth Factor, Type 3