Long-term load duration induces N-cadherin down-regulation and loss of cell phenotype of nucleus pulposus cells in a disc bioreactor culture

Biosci Rep. 2017 Apr 28;37(2):BSR20160582. doi: 10.1042/BSR20160582. Print 2017 Apr 30.

Abstract

Long-term exposure to a mechanical load causes degenerative changes in the disc nucleus pulposus (NP) tissue. A previous study demonstrated that N-cadherin (N-CDH)-mediated signalling can preserve the NP cell phenotype. However, N-CDH expression and the resulting phenotype alteration in NP cells under mechanical compression remain unclear. The present study investigated the effects of the compressive duration on N-CDH expression and on the phenotype of NP cells in an ex vivo disc organ culture. Porcine discs were organ cultured in a self-developed mechanically active bioreactor for 7 days. The discs were subjected to different dynamic compression durations (1 and 8 h at a magnitude of 0.4 MPa and frequency of 1.0 Hz) once per day. Discs that were not compressed were used as controls. The results showed that long-term compression duration (8 h) significantly down-regulated the expression of N-CDH and NP-specific molecule markers (Brachyury, Laminin, Glypican-3 and Keratin 19), attenuated Alcian Blue staining intensity, decreased glycosaminoglycan (GAG) and hydroxyproline (HYP) contents and decreased matrix macromolecule (aggrecan and collagen II) expression compared with the short-term compression duration (1 h). Taken together, these findings demonstrate that long-term load duration can induce N-CDH down-regulation, loss of normal cell phenotype and result in attenuation of NP-related matrix synthesis in NP cells.

Keywords: N-cadherin; compression; degeneration; nucleus pulposus; organ culture.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bioreactors*
  • Cadherins / analysis
  • Cadherins / genetics*
  • Cells, Cultured
  • Down-Regulation*
  • Equipment Design
  • Nucleus Pulposus / cytology*
  • Nucleus Pulposus / metabolism
  • Organ Culture Techniques / instrumentation
  • Phenotype
  • Stress, Mechanical
  • Swine
  • Weight-Bearing

Substances

  • Cadherins