This grant proposal has been submitted in response to RFA-OH-02-004: Musculoskeletal Disorders: Prevention and Treatment, falling under the Biomechanical and Mechanobiology Research bullet. This grant brings together a multidisciplinary research team in the Departments of Biomedical Engineering and Orthopaedic Surgery at Columbia University to develop an animal model that can be used to establish the critical threshold loading level at which degenerative changes are observed in intervertebral discs (IVDs) subjected to cyclic loading under physiologic conditions. Occupational exposures (e.g., overstressed, high repetitive loading, whole body vibration) are generally accepted as an important cause of low back pain reports in industrialized countries. In the United States, back and spine problems represent the second greatest leading cause of disability among persons aged 15 years and older with low back pain from vibration exposure estimated to cost $80 billion annually. To better understand the impact of biomechanical factors on the etiology of disc degeneration, various animal models have introduced mechanical interventions on the spine or tail. These mechanical interventions cause morphologic changes in the intervertebral disc (IVD) and vertebrae similar to degenerative disc disease in humans. Amongst these models, pin instrumented mouse and rat tails have permitted significant insights to the effect of static loading or disuse on disc degeneration. There are,however, apparently no published studies using such models to study applied cyclic loading of the IVD in vivo. To address this apparent gap in spine research, we propose to adapt the in vivo rat tail model currently used by one of the co-Investigators (XE Guo) to study trabecular bone adaptation, to study loading-induced changes in the IVD. In this model, a well-defined loading regiment (static or temporally varying) can be applied to a specific vertebra and its adjacent discs via loading to surgical pins implanted in the neighboring vertebrae. With the ultimate goal of isolating the influence of joint-loading conditions on the response of the IVD, we set forth a number of specific hypotheses and specific aims test our global hypothesis that there exists a range of loading magnitudes and frequencies that will safely maintain normal function and properties of the IVD. Outside of this range, non-physiologic compressive loading (overloading, high frequency, or static loading) of the IVD leads to disc degeneration as measured by decreased material properties (stiffness and modulus) and alterations to expression and levels of aggrecan, type I and II collagen, and cartilage oligomeric protein (COMP).
| Kelly, T-A N; Ng, K W; Ateshian, G A et al. (2009) Analysis of radial variations in material properties and matrix composition of chondrocyte-seeded agarose hydrogel constructs. Osteoarthritis Cartilage 17:73-82 |
| Kelly, Terri-Ann N; Fisher, Matthew B; Oswald, Elizabeth S et al. (2008) Low-serum media and dynamic deformational loading in tissue engineering of articular cartilage. Ann Biomed Eng 36:769-79 |
| Ho, Mandy M; Kelly, Terri-Ann N; Guo, X Edward et al. (2006) Spatially varying material properties of the rat caudal intervertebral disc. Spine (Phila Pa 1976) 31:E486-93 |
| Ishii, Yoshimasa; Thomas, Ashby O; Guo, X Edward et al. (2006) Localization and distribution of cartilage oligomeric matrix protein in the rat intervertebral disc. Spine (Phila Pa 1976) 31:1539-46 |
| Kelly, Terri-Ann N; Ng, Kenneth W; Wang, Christopher C-B et al. (2006) Spatial and temporal development of chondrocyte-seeded agarose constructs in free-swelling and dynamically loaded cultures. J Biomech 39:1489-97 |
