LOAD INDUCED DISC DEGENERATION IN A RAT TAIL MODEL

Summary

Principal Investigator: James Iatridis
Abstract: The proposed K01 project was designed to test important hypotheses while creating an opportunity to increase the candidate's research skills in focal training areas. Dr. Iatridis proposes an intensive training program overseen by an Advisory Board to allow him to progress from mentored to independent scientist. His Advisory Board is comprised of members who are well-recognized for their contributions to biomechanical, computational, and biochemical research on the spine and intervertebral disc. Along with regular meetings with mentors, course work, and seminars, Dr. Iatridis will participate in extended training programs in biochemistry and molecular biology, computational modeling, and magnetic resonance imaging which address specific hypotheses of his research plan and increase his skill base. The long-term goal of the research plan is to isolate mechanical factors that lead to degenerative disc disease and spine pathology. The primary objective of the proposed research is to investigate the effect of mechanical loading conditions applied to the intervertebral disc on the physical signals that cuase a biosynthetic response from the cells and tissue remodeling. Specific aims were developed that are consistent with several future directions for research recommended by the 1995 NIH/AAOS workshop on low back pain and NIH PA97-058. A general hypothetical model is introduced where the intervertebral joint forces are related to dominant load carriage mechanics in the disc tissue and those physical signals that cause a biosynthetic response. The hypotheses test the influence of specific joint forces on on observed intervertebral disc remodeling. External fixators allow precise control over the joint forces applied to a rat tail in vivo. The tail will chronically be exposed to immobilization, low-force compression, high-force compression, and shear loading, as well as loading followed by removal of the fixators to probe for recovery (independent variables). Dependent variables describing the composition and biosynthetic response of the disc tissue will be measured using biochemical, in situ hybridization, and MRI techniques. The mechanical and electrochemical fields in the disc tissue will be calculated using a poroelastic and chemical electric finite element model and mechanical properties measured in this study as input parameters. The biosynthetic response of the disc will be compared to the dominant load carriage mechanisms in the disc tissue in a site-specific manner. This combined experimental and theoretical project provides a framework for future developments on the cell scale by investigating cellular transduction mechanisms, and on the full joint scale by isolating joint forces that may acccelerate intervertebral disc degeneration in human spines.
Funding Period: 1999-09-01 - 2004-07-31
more information: NIH RePORT

Top Publications

  1. ncbi Mechanical damage to the intervertebral disc annulus fibrosus subjected to tensile loading
    James C Iatridis
    Department of Mechanical Engineering, University of Vermont, 231B Votey Building, 33 Colchester Avenue, Burlington, VT 05405 0156, USA
    J Biomech 38:557-65. 2005
  2. ncbi Effect of mechanical loading on mRNA levels of common endogenous controls in articular chondrocytes and intervertebral disk
    Cynthia R Lee
    Biochemistry and Cell Biology, AO Research Institute, Davos, Switzerland
    Anal Biochem 341:372-5. 2005
  3. ncbi Assessment of compressive modulus, hydraulic permeability and matrix content of trypsin-treated nucleus pulposus using quantitative MRI
    D Perie
    Department of Mechanical Engineering, University of Vermont, Burlington VT, USA
    J Biomech 39:1392-400. 2006
  4. ncbi The effects of short-term load duration on anabolic and catabolic gene expression in the rat tail intervertebral disc
    Jeffery J Maclean
    Department of Mechanical Engineering, University of Vermont, Burlington, VT 05405 0156, USA
    J Orthop Res 23:1120-7. 2005
  5. ncbi Confined compression experiments on bovine nucleus pulposus and annulus fibrosus: sensitivity of the experiment in the determination of compressive modulus and hydraulic permeability
    Delphine Périé
    Department of Mechanical Engineering, University of Vermont, Burlington, VT, USA
    J Biomech 38:2164-71. 2005
  6. pmc Correlating material properties with tissue composition in enzymatically digested bovine annulus fibrosus and nucleus pulposus tissue
    Delphine S Perie
    Department of Mechanical Engineering, University of Vermont, Burlington, VT, USA
    Ann Biomed Eng 34:769-77. 2006

Scientific Experts

Detail Information

Publications6

  1. ncbi Mechanical damage to the intervertebral disc annulus fibrosus subjected to tensile loading
    James C Iatridis
    Department of Mechanical Engineering, University of Vermont, 231B Votey Building, 33 Colchester Avenue, Burlington, VT 05405 0156, USA
    J Biomech 38:557-65. 2005
    ....
  2. ncbi Effect of mechanical loading on mRNA levels of common endogenous controls in articular chondrocytes and intervertebral disk
    Cynthia R Lee
    Biochemistry and Cell Biology, AO Research Institute, Davos, Switzerland
    Anal Biochem 341:372-5. 2005
  3. ncbi Assessment of compressive modulus, hydraulic permeability and matrix content of trypsin-treated nucleus pulposus using quantitative MRI
    D Perie
    Department of Mechanical Engineering, University of Vermont, Burlington VT, USA
    J Biomech 39:1392-400. 2006
    ....
  4. ncbi The effects of short-term load duration on anabolic and catabolic gene expression in the rat tail intervertebral disc
    Jeffery J Maclean
    Department of Mechanical Engineering, University of Vermont, Burlington, VT 05405 0156, USA
    J Orthop Res 23:1120-7. 2005
    ....
  5. ncbi Confined compression experiments on bovine nucleus pulposus and annulus fibrosus: sensitivity of the experiment in the determination of compressive modulus and hydraulic permeability
    Delphine Périé
    Department of Mechanical Engineering, University of Vermont, Burlington, VT, USA
    J Biomech 38:2164-71. 2005
    ....
  6. pmc Correlating material properties with tissue composition in enzymatically digested bovine annulus fibrosus and nucleus pulposus tissue
    Delphine S Perie
    Department of Mechanical Engineering, University of Vermont, Burlington, VT, USA
    Ann Biomed Eng 34:769-77. 2006
    ..Correlation coefficients r<or=0.75 for the multiple regression indicated water and GAG content can moderately predict material properties, however other compositional and structural factors must be considered...