Intervertebral disc degeneration is a debilitating disorder of the spine, but the mechanisms involved in its initiation and progression are largely unknown. Certain compressive loading regimens have been shown to induce apoptosis and irreversible disc degeneration, while others do not. Some theories postulate that the effects of loading are dependent on time-history stress (or strain). In support of this, studies have shown that there can be benefits associated with specific levels of mechanical stimulation in musculoskeletal tissues. Based on preliminary and published data, we hypothesize the existence of a metabolic zone within which disc degeneration is inhibited. We expect that the borders of this zone will be defined by the hydrostatic and deviatoric stress histories of the annulus fibrosus and nucleus pulposus, respectively. Furthermore, we hypothesize that certain regimens of dynamic spinal bending motions can maintain a favorable time-history mechanical stress. Parametric analyses using a poro-hyperelastic finite element model of the disc will be performed to predict stress histories in order to define a set of candidate bending regimens for preventing disc degeneration. These regimens will then be tested experimentally to determine the effects on biosynthesis and apoptosis.

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
5F32AR048033-03
Application #
6630379
Study Section
Oral Biology and Medicine Subcommittee 1 (OBM)
Program Officer
Panagis, James S
Project Start
2002-08-03
Project End
2004-08-02
Budget Start
2003-08-03
Budget End
2004-08-02
Support Year
3
Fiscal Year
2003
Total Cost
$48,148
Indirect Cost
Name
University of California San Francisco
Department
Orthopedics
Type
Schools of Medicine
DUNS #
094878337
City
San Francisco
State
CA
Country
United States
Zip Code
94143
Lotz, Jeffrey C; Hadi, Tamer; Bratton, Clayton et al. (2008) Anulus fibrosus tension inhibits degenerative structural changes in lamellar collagen. Eur Spine J 17:1149-59
Shogren, Kristen L; Turner, Russell T; Yaszemski, Michael J et al. (2007) Double-stranded RNA-dependent protein kinase is involved in 2-methoxyestradiol-mediated cell death of osteosarcoma cells. J Bone Miner Res 22:29-36
Hsieh, Adam H; Wagner, Diane R; Cheng, Louis Y et al. (2005) Dependence of mechanical behavior of the murine tail disc on regional material properties: a parametric finite element study. J Biomech Eng 127:1158-67
Hsieh, Adam H; Lotz, Jeffrey C (2003) Prolonged spinal loading induces matrix metalloproteinase-2 activation in intervertebral discs. Spine (Phila Pa 1976) 28:1781-8