This study evaluated how dynamic compression induced changes in gene expression, tissue composition, and structural properties of the intervertebral disc using a rat tail model. We hypothesized that daily exposure to dynamic compression for short durations would result in anabolic remodeling with increased matrix protein expression and proteoglycan content, and that increased daily load exposure time and experiment duration would retain these changes but also accumulate changes representative of mild degeneration. Sprague-Dawley rats (n ¼ 100) were instrumented with an Ilizarov-type device and divided into three dynamic compression (2 week-1.5 h/day, 2 week-8 h/day, 8 week-8 h/day at 1 MPa and 1 Hz) and two sham (2 week, 8 week) groups. Dynamic compression resulted in anabolic remodeling with increased matrix mRNA expression, minimal changes in catabolic genes or disc structure and stiffness, and increased glysosaminoglycans (GAG) content in the nucleus pulposus. Some accumulation of mild degeneration with 8 week-8 h included loss of annulus fibrosus GAG and disc height although 8-week shams also had loss of disc height, water content, and minor structural alterations. We conclude that dynamic compression is consistent with a notion of ''healthy'' loading that is able to maintain or promote matrix biosynthesis without substantially disrupting disc structural integrity. A slow accumulation of changes similar to human disc degeneration occurred when dynamic compression was applied for excessive durations, but this degenerative shift was mild when compared to static compression, bending, or other interventions that create greater structural disruption. Keywords: intervertebral disc; disc degeneration; mechanobiology; animal model; biomechanics Substantial socioeconomic problems that result from low back pain are often associated with intervertebral disc (IVD) degeneration.1 The etiology of disc degeneration is complex and multifactorial with heredity, mechanical loading, and nutrition all playing significant roles.2-7 These contributing factors are interactive and strongly affected by aging. For example, degradation of the molecular structure of the disc during aging can also render it more susceptible to mechanical injuries. 4 Loading type, magnitude, duration, and frequency all influence cell metabolic responses and matrix remodeling. 5,8,9 Mechanical loading may induce remodeling directly via tissue stresses that may predispose the matrix to damage or through alterations in the biosynthetic response due to mechanically altered biosynthesis of proteins and enzymes.8 IVD degeneration is manifested morphologically through a loss in disc height, decreased nucleus volume, and in a loss of distinction between nucleus pulposus (NP) and annulus fibrosus (AF). In more severe degeneration, a more extensive loss in IVD structural organization has been noted, with formation of clefts and tears in the AF.2 Degenerative changes on the biochemical level are noted first in the NP, with a loss of glysosaminoglycans (GA...
Enzymatic treatments were applied to rat motion segments to establish structure–function relationships and determine mechanical parameters most sensitive to simulated remodeling and degeneration. Rat caudal and lumbar disc biomechanical behaviors were evaluated to improve knowledge of their similarities and differences due to their frequent use during in vivo models. Caudal motion segments were assigned to four groups: soaked (control), genipin treated, elastase treated, and collagenase treated. Fresh lumbar and caudal discs were also compared. The mechanical protocol involved five force-controlled loading stages: equilibration, cyclic compression-tension, quasi-static compression, frequency sweep, and creep. Crosslinking was found to have the greatest effect on IVD properties at resting stress. Elastin's role was greatest in tension and at higher force conditions, where GAG content was also a contributing factor. Collagenase treatment caused tissue compaction, which impacted mechanical properties at both high and low force conditions. Equilibration creep and cyclic compression-tension tests were the mechanical tests most sensitive to alterations in specific matrix constituents. Caudal and lumbar motion segments had many similarities but biomechanical differences suggested some distinctions in collagenous structure and water transport characteristics in addition to the geometric differences. Results provide a basis for interpreting biomechanical changes observed in animal model studies of degeneration and remodeling, and underscore the need to maintain and/or repair collagen integrity in IVD health and disease.
Study Design-In vitro and in vivo rat tail model to assess effects of torsion on intervertebral disc biomechanics and gene expression.Objective-Investigate effects of torsion on promoting biosynthesis and producing injury in rat caudal intervertebral discs.Summary of Background Data-Torsion is an important loading mode in the disc and increased torsional range of motion is associated with clinical symptoms from disc disruption. Altered elastin content is implicated in disc degeneration, but its effects on torsional loading are unknown. Although effects of compression have been studied, the effect of torsion on intervertebral disc gene expression is unknown.Methods-In vitro biomechanical tests were performed in torsion on rat tail motion segments subjected to 4 treatments: elastase, collagenase, genipin, control. In vivo tests were performed on rats with Ilizarov-type fixators implanted to caudal motion segments with five 90-minute loading groups: 1 Hz cyclic torsion to ±5°, ±15°, and ±30°, static torsion to +30°, and sham. Anulus and nucleus tissues were separately analyzed using qRT-PCR for gene expression of anabolic, catabolic, and proinflammatory cytokine markers.Results-In vitro tests showed decreased torsional stiffness following elastase treatment and no changes in stiffness with frequency. In vivo tests showed no significant changes in dynamic stiffness with time. Cyclic torsion upregulated elastin expression in the anulus fibrosus. Upregulation of TNF-α and IL-1β was measured at ±30°.Conclusion-We conclude that strong differences in the disc response to cyclic torsion and compression are apparent with torsion increasing elastin expression and compression resulting in a more substantial increase in disc metabolism in the nucleus pulposus. Results highlight the importance of elastin in torsional loading and suggest that elastin remodels in response to shearing. Torsional loading can cause injury to the disc at excessive amplitudes that are detectable biologically before they are biomechanically. ©2010, Lippincott Williams & WilkinsAddress correspondence and reprint requests to James C. Iatridis, PhD, University of Vermont, 33 Colchester Ave, 201 Perkins Hall, Burlington, VT 05405; James.iatridis@uvm.edu. NIH Public AccessAuthor Manuscript Spine (Phila Pa 1976 The causes of intervertebral disc (IVD) degeneration are multifaceted, with contributions from aging, mechanical, genetic, and nutritional factors. 1 IVD degeneration is manifested biochemically through a loss of glycosaminoglycans, regional changes in collagen matrix composition 2 as well as changes in elastin structure 3,4 and content. 5 An increase in expression of proteases and their inhibitors, 6,7 including MMP-3, ADAMTS-4, and TIMP-1 as well as cytokines IL-1β 8 and TNF-α 9 have also been associated with degeneration. Biomechanically, IVD degeneration is characterized by a decrease in intradiscal and osmotic pressure, 10,11 an altered range of motion and reduced neutral zone, 12-14 and a decrease in creep and creep rate. 15,16 Although...
The aim of this study was to assess the ability of lower limb surrogates to predict injury due to floor/foot plate impact in military vehicles during anti-vehicular land mine explosions. Testing was conducted using two loading conditions simulated to represent those conditions created in the field. The lower condition was represented by a 24-kg mass impactor with a velocity of 4.7 m/s. The higher loading condition was represented by a 37-kg mass impactor with a velocity of 8.3 m/s. Two biomechanical surrogates were evaluated using the loading conditions: 50th percentile Hybrid III foot/ankle and Test Device for Human Occupant Restraint THOR-Lx. Comparisons of the force-time response were made to established corridors. Results show a better correlation to the corridors with the THOR-Lx; however, future improvements to the THOR-Lx are recommended.
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