The Effect of Compressive Force Applied to the Intervertebral Disc in Vivo

Hutton, William; Toribatake, Yasumitsu; Elmer, William A.; Ganey, Timothy; Tomita, Katsuro; Whitesides, Thomas E.

doi:10.1097/00007632-199812010-00007

Cited by 133 publications

(74 citation statements)

References 46 publications

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“…Other work has shown increased collagen type I expression and decreased collagen type II expression in canine intervertebral discs subjected to high axial compressive forces in vivo. 64 Similar to the present study, axial compressive loading has been predicted via FEA to translate into both tensile and compressive strains within the three-dimensional structure of the intervertebral disc. 65 Increased passive axial compressive loading levels, therefore, may have helped to drive the development of a more fibrocartilaginous engineered matrix expressing both collagen types I and II.…”

Section: Discussionsupporting

confidence: 59%

Passive Strain-Induced Matrix Synthesis and Organization in Shape-Specific, Cartilaginous Neotissues

MacBarb

Paschos

Abeug

et al. 2014

Tissue Engineering Part A

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Tissue-engineered musculoskeletal soft tissues typically lack the appropriate mechanical robustness of their native counterparts, hindering their clinical applicability. With structure and function being intimately linked, efforts to capture the anatomical shape and matrix organization of native tissues are imperative to engineer functionally robust and anisotropic tissues capable of withstanding the biomechanically complex in vivo joint environment. The present study sought to tailor the use of passive axial compressive loading to drive matrix synthesis and reorganization within self-assembled, shape-specific fibrocartilaginous constructs, with the goal of developing functionally anisotropic neotissues. Specifically, shape-specific fibrocartilaginous neotissues were subjected to 0, 0.01, 0.05, or 0.1 N axial loads early during tissue culture. Results found the 0.1-N load to significantly increase both collagen and glycosaminoglycan synthesis by 27% and 67%, respectively, and to concurrently reorganize the matrix by promoting greater matrix alignment, compaction, and collagen crosslinking compared with all other loading levels. These structural enhancements translated into improved functional properties, with the 0.1-N load significantly increasing both the relaxation modulus and Young's modulus by 96% and 255%, respectively, over controls. Finite element analysis further revealed the 0.1-N uniaxial load to induce multiaxial tensile and compressive strain gradients within the shape-specific neotissues, with maxima of 10.1%, 18.3%, and -21.8% in the XX-, YY-, and ZZ-directions, respectively. This indicates that strains created in different directions in response to a single axis load drove the observed anisotropic functional properties. Together, results of this study suggest that strain thresholds exist within each axis to promote matrix synthesis, alignment, and compaction within the shape-specific neotissues. Tailoring of passive axial loading, thus, presents as a simple, yet effective way to drive in vitro matrix development in shape-specific neotissues toward more closely achieving native structural and functional properties.

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Section: Discussionsupporting

confidence: 59%

Passive Strain-Induced Matrix Synthesis and Organization in Shape-Specific, Cartilaginous Neotissues

MacBarb

Paschos

Abeug

et al. 2014

Tissue Engineering Part A

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“…An increase of collagen type I is commonly encountered in degenerating discs in vivo. [47][48][49][50][51] Using immunohistochemistry, Le Maitre et al 52 demonstrated the same pattern of collagen types in an unconstrained culture of human discs. Two independent investigations on rabbit disc stab models also demonstrated a degenerative matrix gene expression in the postinterventional course.…”

Section: Discussionmentioning

confidence: 91%

Influence of diurnal hyperosmotic loading on the metabolism and matrix gene expression of a whole‐organ intervertebral disc model

Haschtmann

Stoyanov

Ferguson

2006

Journal Orthopaedic Research

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It is generally agreed that the mechanical environment of intervertebral disc cells plays an important role in maintaining a balanced matrix metabolism. The precise mechanism by which the signals are transduced into the cells is poorly understood. Osmotic changes in the extracellular matrix (ECM) are thought to be involved. Current in-vitro studies on this topic are mostly short-term and show conflicting data on the reaction of disc cells subjected to osmotic changes which is partially due to the heterogenous and often substantially-reduced culture systems. The aim of the study was therefore to investigate the effects of cyclic osmotic loading for 4 weeks on metabolism and matrix gene expression in a full-organ intervertebral disc culture system. Intervertebral disc/endplate units were isolated from New Zealand White Rabbits and cultured either in iso-osmotic media (335 mosmol/kg) or were diurnally exposed for 8 hours to hyper-osmotic conditions (485 mosmol/kg). Cell viability, metabolic activity, matrix composition and matrix gene expression profile (collagen types I/II and aggrecan) were monitored using Live/Dead cell viability assay, tetrazolium reduction test (WST 8), proteoglycan and DNA quantification assays and quantitative PCR. The results show that diurnal osmotic stimulation did not have significant effects on proteoglycan content, cellularity and disc cell viability after 28 days in culture. However, hyperosmolarity caused increased cell death in the early culture phase and counteracted upregulation of type I collagen gene expression in nucleus and annulus cells. Moreover, the initially decreased cellular dehydrogenase activity recovered with osmotic stimulation after 4 weeks and aggrecan gene down-regulation was delayed, although the latter was not significant according to our statistical criteria. In contrast, collagen type II did not respond to the osmotic changes and was downregulated in both groups. In conclusion, diurnal hyper-osmotic stimulation of a whole-organ disc/ endplate culture partially inhibits a matrix gene expression profile as encountered in degenerative disc disease and counteracts cellular metabolic hypo-activity. ß

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“…Over the last few decades, several studies have shown that changes in the mechanical environment of the disc can result in remodeling, breakdown, and reorganization of the extracellular matrix [ 1, 7,13,[18][19][20][21][22]29,32,33,35,41,44], leading in some cases to signs of accelerated disc degeneration. Such work forms the *Corresponding author.…”

Section: Introductionmentioning

confidence: 99%

“…Immobilization and static compression have been shown to induce cell apoptosis and alter mechanical properties (disc thickness, axial compliance and angular laxity), matrix content (proteoglycan and type I and I1 collagen), metalloproteinase activity, and disc cell gene expression (aggrecan and collagen-11) [ 17, [20][21][22][23]29,32]. With respect to the more physiological dynamic loads, Ching et al recently reported that two weeks of dynamic loading of the rat tail intervertebral disc led to a decrease in disc angular compliance, an increase in angular laxity, and a frequency -dependent decrease in disc height [$I.…”

mentioning

confidence: 99%

Anabolic and catabolic mRNA levels of the intervertebral disc vary with the magnitude and frequency of in vivo dynamic compression

MacLean

Lee

Alini

et al. 2004

Journal Orthopaedic Research

170

181

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The goal of this study was to characterize the anabolic and catabolic mRNA response of the disc to dynamic loading to determine if variations in the magnitude and/or frequency of loading could elicit different cellular responses. Sixty-eight Wistar rats were instrumented with an Ilizarov-type device spanning caudal disc 8-9. Seventy-two hours after surgery, animals were anesthetized and loaded at either 1 or 0.2 MPa at a frequency of 1, 0.2 or 0.01 Hz for 2 h (6 groups). The surgical control (Sham) animals underwent anesthesia with no loading. Loaded (c8-9) and internal-control discs (c6-7 and c10-11) were dissected and annulus and nucleus tissue were separately analyzed by real-time RT-PCR for levels of anabolic (collagen-1 A1 , collagen-2A1, aggrecan) and catabolic (MMP-3, MMP-13, ADAMTs-4) mRNA. In the nucleus, a frequency-dependent response was seen at 1 MPa with anabolic genes stimulated at 0.01 Hz and catabolic genes at 1 Hz. In the annulus all frequencies resulted in significant up-regulation of catabolic mRNA at 1 MPa loading. In general loading at 0.2 MPa or 0.2 Hz had little effect on gene expression. The results suggest that gene expression of the annulus appears to be more dependent on the magnitude of applied stress, while the nucleus is both magnitude-and frequency-dependent.

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The Effect of Compressive Force Applied to the Intervertebral Disc in Vivo

Abstract: A high compressive force applied to the disc over a period of time initiates changes in proteoglycans and collagen.

Cited by 133 publications

References 46 publications

Passive Strain-Induced Matrix Synthesis and Organization in Shape-Specific, Cartilaginous Neotissues

Passive Strain-Induced Matrix Synthesis and Organization in Shape-Specific, Cartilaginous Neotissues

Influence of diurnal hyperosmotic loading on the metabolism and matrix gene expression of a whole‐organ intervertebral disc model

Anabolic and catabolic mRNA levels of the intervertebral disc vary with the magnitude and frequency of in vivo dynamic compression

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