Mechanisms of Load-Induced Intervertebral Disc Degeneration

Back pain and its associated disabilities are a major source of economic burden in the United States. It has been reported as the leading cause of disability in the working-age group. With almost 70% of the population experiencing low back pain during their lifetime, there is an urgent need to discover the etiology of this disease.

The overall goal of this dissertation was to characterize specific mechanisms of mechanically induced intervertebral disc degeneration. Research has speculated that traumatic loading can initiate disc degeneration and lead to low back pain; however, it has proven difficult to identify the source of degeneration and, more importantly, separate its effects from associated co-morbidities. Therefore, I developed a series of hypotheses to address the biomechanics, biochemical response and cellular architectural response to traumatic static loading. I first hypothesized that the disc’s ability to resist creep is significantly affected by load-induced degeneration. Second, I proposed that static overloading of the intervertebral disc triggers a cascade of native inflammatory and degenerative molecules that contribute to tissue degeneration. Finally, I inquired how disc cellular architecture and morphology are affected by static overloading and whether these effects are time and load-dependent.

I observed that during moderate load-induced degeneration, discs lose height, increase in proteoglycan content, become less stiff and creep more. Furthermore I observed that excessive compressive loading can induce native cytokine production within the intervertebral disc and that the production is time-dependent. Finally, I demonstrated that injurious tissue level compression deforms nucleus and annular cells differently due to variability in spatial location and matrix content and that changes in load magnitude and duration alter the morphological response of the cells. In conclusion, this dissertation research sheds new light onto the role of compressive loading in intervertebral disc degeneration and may provide direction into targeted therapies for low back pain and improved occupational guidelines for maintaining disc health.

Year	Entry
1998	Lotz JC, Colliou OK, Chin JR, Duncan NA, Liebenberg E. Compression-induced degeneration of the intervertebral disc: an in vivo mouse model and finite-element study. Spine. December 1, 1998;23(23):2493-2506.
1995	Klein-Nulend J, van der Plas A, Semeins CM, Ajubi NE, Frangos JA, Nijweide PJ, Burger EH. Sensitivity of osteocytes to biomechanical stress in vitro. FASEB J. March 1995;9(5):441-445.
1998	Quinn TM, Grodzinsky AJ, Buschmann MD, Kim YJ, Hunziker EB. Mechanical compression alters proteoglycan deposition and matrix deformation around individual cells in cartilage explants. J Cell Sci. March 1998;111(5):573-583.
1993	Wang N, Butler JP, Ingber DE. Mechanotransduction across the cell surface and through the cytoskeleton. Science. May 21, 1993;260(5111):1124-1127.
1999	Guilak F, Ting-Beall HP, Baer AE, Trickey WR, Erickson GR, Setton LA. Viscoelastic properties of intervertebral disc cells: identification of two biomechanically distinct cell populations. Spine. December 1, 1999;24(23):2475-2483.
1995	Guilak F, Ratcliffe A, Mow VC. Chondrocyte deformation and local tissue strain in articular cartilage: a confocal microscopy study. J Orthop Res. May 1995;13(3):410-421.
1996	Buschmann MD, Hunziker EB, Kim YJ, Grodzinsky AJ. Altered aggrecan synthesis correlates with cell and nucleus structure in statically compressed cartilage. J Cell Sci. February 1996;109(2):499-508.
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Year

Entry

1998

Lotz JC, Colliou OK, Chin JR, Duncan NA, Liebenberg E. Compression-induced degeneration of the intervertebral disc: an in vivo mouse model and finite-element study. Spine. December 1, 1998;23(23):2493-2506.

1995

Klein-Nulend J, van der Plas A, Semeins CM, Ajubi NE, Frangos JA, Nijweide PJ, Burger EH. Sensitivity of osteocytes to biomechanical stress in vitro. FASEB J. March 1995;9(5):441-445.

1998

Quinn TM, Grodzinsky AJ, Buschmann MD, Kim YJ, Hunziker EB. Mechanical compression alters proteoglycan deposition and matrix deformation around individual cells in cartilage explants. J Cell Sci. March 1998;111(5):573-583.

1993

Wang N, Butler JP, Ingber DE. Mechanotransduction across the cell surface and through the cytoskeleton. Science. May 21, 1993;260(5111):1124-1127.

1999

Guilak F, Ting-Beall HP, Baer AE, Trickey WR, Erickson GR, Setton LA. Viscoelastic properties of intervertebral disc cells: identification of two biomechanically distinct cell populations. Spine. December 1, 1999;24(23):2475-2483.