? Intervertebral disc degeneration and associated discogenic back pain continue to represent major national health concerns. However, the mechanisms that drive the initiation and progression of disc degeneration are elusive, mainly because identifying the early cellular and molecular events leading to the presentation of symptoms is not feasible. Rodent tail disc loading models that have recently emerged to study the effects of mechanical stress on disc health have vast potential for elucidating the underlying mechanisms of degeneration. However, there remain questions as to the validity of rodent tail discs as a biomechanical analogue of human discs. Our central hypothesis is that the internal mechanics of rodent tail discs are similar to those of human discs. This project aims to test this hypothesis by measuring intradiscal pressures - as a parameter indicative of internal disc mechanics - in healthy and degenerate rat caudal discs both in vitro and in vivo. Specifically, our proposed work utilizes a novel micro-optical sensor to record intradiscal pressure in rat tail discs, data that have not previously been possible to obtain due to size constraints. Using an in vivo rodent tail loading model and an annular incision injury model, we will characterize intradiscal pressure-external load relationships of discs at various stages of degeneration in Specific Aim 1. These relationships obtained from isolated motion segments can then be compared with those reported for human motion segments in order to validate the continued use of rodent tail disc models for studying the role of mechanical stress on disc degeneration. As a related concern, the loads applied in rodent tail models in vivo have not been verified to produce stress/strain that is comparable to that experienced by human discs under normal physical activity. Thus, the level of cellular stimulation governed by the internal mechanics of the disc may not be physiologically accurate.
Specific Aim 2 will measure intradiscal pressure in rat tail discs in vivo during the application of mechanical loading regimens typically used in these animal studies. Measuring the pressures generated in loaded rat discs in vivo will be crucial for future experimental design for both animal and cell culture models. ? ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Small Research Grants (R03)
Project #
5R03AR054051-02
Application #
7405389
Study Section
Special Emphasis Panel (ZAR1-EHB-H (J1))
Program Officer
Tyree, Bernadette
Project Start
2007-04-15
Project End
2010-02-28
Budget Start
2008-03-01
Budget End
2009-02-28
Support Year
2
Fiscal Year
2008
Total Cost
$72,765
Indirect Cost
Name
University of Maryland College Park
Department
Engineering (All Types)
Type
Schools of Engineering
DUNS #
790934285
City
College Park
State
MD
Country
United States
Zip Code
20742
Rastogi, Anshu; Kim, Hyunchul; Twomey, Julianne D et al. (2013) MMP-2 mediates local degradation and remodeling of collagen by annulus fibrosus cells of the intervertebral disc. Arthritis Res Ther 15:R57
Hwang, David; Gabai, Adam S; Yu, Miao et al. (2012) Role of load history in intervertebral disc mechanics and intradiscal pressure generation. Biomech Model Mechanobiol 11:95-106
Wang, Ping; Yang, Li; Hsieh, Adam H (2011) Nucleus pulposus cell response to confined and unconfined compression implicates mechanoregulation by fluid shear stress. Ann Biomed Eng 39:1101-11
Hsieh, Adam H; Twomey, Julianne D (2010) Cellular mechanobiology of the intervertebral disc: new directions and approaches. J Biomech 43:137-45
Hsieh, Adam H; Hwang, David; Ryan, David A et al. (2009) Degenerative anular changes induced by puncture are associated with insufficiency of disc biomechanical function. Spine (Phila Pa 1976) 34:998-1005
Nesson, Silas; Yu, Miao; Zhang, Xuming et al. (2008) Miniature fiber optic pressure sensor with composite polymer-metal diaphragm for intradiscal pressure measurements. J Biomed Opt 13:044040