In vivo remodeling of intervertebral discs in response to short‐ and long‐term dynamic compression

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 = 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. © 2009 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res

[1]  Keita Ito,et al.  Effects of Immobilization and Dynamic Compression on Intervertebral Disc Cell Gene Expression In Vivo , 2003, Spine.

[2]  Luke Windisch,et al.  Vertebral Height Growth Predominates Over Intervertebral Disc Height Growth in Adolescents With Scoliosis , 2006, Spine.

[3]  M. Battié,et al.  Lumbar disc degeneration: epidemiology and genetics. , 2006, The Journal of bone and joint surgery. American volume.

[4]  J. Lotz,et al.  Compression-induced degeneration of the intervertebral disc: an in vivo mouse model and finite-element study. , 1998, Spine.

[5]  J. Urban,et al.  Nutrition of the Intervertebral Disc , 2004, Spine.

[6]  J. Ralphs,et al.  Are animal models useful for studying human disc disorders/degeneration? , 2007, European Spine Journal.

[7]  J. Lotz,et al.  Intervertebral Disc Cell Death Is Dependent on the Magnitude and Duration of Spinal Loading , 2000, Spine.

[8]  Mauro Alini,et al.  The effects of short‐term load duration on anabolic and catabolic gene expression in the rat tail intervertebral disc , 2005, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.

[9]  Ellen Liebenberg,et al.  Biological and mechanical consequences of transient intervertebral disc bending , 2007, European Spine Journal.

[10]  I A Stokes,et al.  Compression-induced changes in intervertebral disc properties in a rat tail model. , 1999, Spine.

[11]  J. Laible,et al.  Direct measurement of intervertebral disc maximum shear strain in six degrees of freedom: motions that place disc tissue at risk of injury. , 2007, Journal of biomechanics.

[12]  Christopher J Hunter,et al.  Cytomorphology of notochordal and chondrocytic cells from the nucleus pulposus: a species comparison , 2004, Journal of anatomy.

[13]  M M Panjabi,et al.  Disc Degeneration Affects the Multidirectional Flexibility of the Lumbar Spine , 1994, Spine.

[14]  Mauro Alini,et al.  Anabolic and catabolic mRNA levels of the intervertebral disc vary with the magnitude and frequency of in vivo dynamic compression , 2004, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.

[15]  Dawn M. Elliott,et al.  Comparison of Animals Used in Disc Research to Human Lumbar Disc Geometry , 2007, Spine.

[16]  J. Lotz,et al.  The effect of static in vivo bending on the murine intervertebral disc. , 2001, The spine journal : official journal of the North American Spine Society.

[17]  P. Ragan,et al.  Down‐regulation of chondrocyte aggrecan and type‐II Collagen gene expression correlates with increases in static compression magnitude and duration , 1999, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.

[18]  Justin Stinnett-Donnelly,et al.  A Removable Precision Device for In-Vivo Mechanical Compression of Rat Tail Intervertebral Discs , 2007 .

[19]  J. Matyas,et al.  The notochordal cell in the nucleus pulposus: a review in the context of tissue engineering. , 2003, Tissue engineering.

[20]  W C Hutton,et al.  The effect of hydrostatic pressure on intervertebral disc metabolism. , 1999, Spine.

[21]  L. Setton,et al.  Mechanobiology of the intervertebral disc and relevance to disc degeneration. , 2006, The Journal of bone and joint surgery. American volume.

[22]  M. Adams,et al.  What is Intervertebral Disc Degeneration, and What Causes It? , 2006, Spine.

[23]  P. Roughley Biology of Intervertebral Disc Aging and Degeneration: Involvement of the Extracellular Matrix , 2004, Spine.

[24]  James D. Kang,et al.  Introduction: disc degeneration: summary. , 2004, Spine.

[25]  N Bogduk,et al.  The pathophysiology of disc degeneration: a critical review. , 2008, The Journal of bone and joint surgery. British volume.

[26]  Jeffrey C Lotz,et al.  Animal Models of Intervertebral Disc Degeneration: Lessons Learned , 2004, Spine.

[27]  S. A. Shirazi-Adl,et al.  Nutrient supply and intervertebral disc metabolism. , 2006, The Journal of bone and joint surgery. American volume.

[28]  J. Ralphs,et al.  Extracellular matrix in development of the intervertebral disc. , 2001, Matrix biology : journal of the International Society for Matrix Biology.

[29]  J. Iatridis,et al.  In vivo intervertebral disc remodeling: Kinetics of mRNA expression in response to a single loading event , 2008, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.

[30]  Jeffrey C Lotz,et al.  Prolonged Spinal Loading Induces Matrix Metalloproteinase-2 Activation in Intervertebral Discs , 2003, Spine.

[31]  J. Iatridis,et al.  Effect of mechanical loading on mRNA levels of common endogenous controls in articular chondrocytes and intervertebral disk. , 2005, Analytical biochemistry.

[32]  Mauro Alini,et al.  Effects of mechanical loading on intervertebral disc metabolism in vivo. , 2006, The Journal of bone and joint surgery. American volume.

[33]  W C Hutton,et al.  Do the intervertebral disc cells respond to different levels of hydrostatic pressure? , 2001, Clinical biomechanics.

[34]  Ian A. F. Stokes,et al.  Mechanical Conditions That Accelerate Intervertebral Disc Degeneration: Overload Versus Immobilization , 2004, Spine.

[35]  W. Erwin,et al.  Notochord Cells Regulate Intervertebral Disc Chondrocyte Proteoglycan Production and Cell Proliferation , 2006, Spine.

[36]  D. Buttle,et al.  Improved quantitation and discrimination of sulphated glycosaminoglycans by use of dimethylmethylene blue. , 1986, Biochimica et biophysica acta.

[37]  W. Hutton,et al.  The Effect of Compressive Force Applied to the Intervertebral Disc in Vivo: A Study of Proteoglycans and Collagen , 1998, Spine.

[38]  Achim Elfering,et al.  Effect of aging and degeneration on disc volume and shape: A quantitative study in asymptomatic volunteers , 2006, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.