Effect of limited nutrition on in situ intervertebral disc cells under simulated-physiological loading

Spine (Phila Pa 1976). 2009 May 20;34(12):1264-71. doi: 10.1097/BRS.0b013e3181a0193d.

Abstract

Study design: Whole ovine caudal intervertebral discs (IVD) were cultured in sufficient and limited nutrition under simulated-physiologic loading for 7 and 21 days.

Objective: To study the effect of limited nutrition on disc cells embedded in their native tissue in short- and midterm whole organ disc culture.

Summary of background data: Nutrient-limited induction of disc cell death in vitro has been demonstrated and is believed to be a factor in disc degeneration. Nutrient-limited cell death and its consequences, as it relates to degeneration, have not been investigated in the intact IVD.

Methods: Ovine IVDs with endplates were cultured for 7 and 21 days under simulated-physiologic loading, either in media with limited (2 g/L) or sufficient (4.5 g/L) glucose concentration. Cell viability, relative gene expression, newly synthesized chondroitin sulfate content, and matrix metalloproteinase (MMP) activity were measured after culture and compared to fresh tissue.

Results: In sufficient glucose media, cell viability was maintained through 7 days to 21 days of culture. In limited glucose, it dropped significantly to 62% in the anulus fibrosus and to 56% in the nucleus pulposus after 7 days and remained so until 21 days (63% in the anulus fibrosus and 52% in the nucleus pulposus). No significant differences were found between culture conditions for relative gene expression, newly synthesized chondroitin sulfate and inactive and active forms of MMP13 and MMP7.

Conclusion: With this culture system, whole IVD explants could be maintained up to 21 days. Cell viability decreased to 50% to 60% under limited nutrition within days and remained so up to 3 weeks. The surviving cells did not compensate matrix production in this time frame.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Death / physiology
  • Cell Survival / physiology
  • Chondrocytes / metabolism*
  • Chondrocytes / pathology
  • Chondroitin Sulfates / biosynthesis
  • Chondroitin Sulfates / genetics
  • Compressive Strength / physiology
  • Extracellular Matrix / genetics
  • Extracellular Matrix / metabolism
  • Fibrocartilage / metabolism*
  • Fibrocartilage / pathology
  • Fibrocartilage / physiopathology
  • Gene Expression / physiology
  • Glucose / deficiency*
  • Intervertebral Disc / metabolism*
  • Intervertebral Disc / pathology
  • Intervertebral Disc / physiopathology
  • Intervertebral Disc Displacement / etiology
  • Intervertebral Disc Displacement / metabolism*
  • Intervertebral Disc Displacement / physiopathology
  • Ischemia / complications
  • Ischemia / metabolism*
  • Ischemia / physiopathology
  • Matrix Metalloproteinases / biosynthesis
  • Matrix Metalloproteinases / genetics
  • Organ Culture Techniques / methods
  • Sheep, Domestic
  • Weight-Bearing / physiology

Substances

  • Chondroitin Sulfates
  • Matrix Metalloproteinases
  • Glucose