In vivo remodeling of intervertebral discs in response to short- and long-term dynamic compression
Karin Wuertz
Spine Bioengineering Lab, School of Engineering, University of Vermont, 33 Colchester Avenue, 201 Perkins Hall, Burlington, Vermont 05405
Spine Research Unit, University Hospital Balgrist, University of Zurich, Zurich, Switzerland
Search for more papers by this authorKarolyn Godburn
Spine Bioengineering Lab, School of Engineering, University of Vermont, 33 Colchester Avenue, 201 Perkins Hall, Burlington, Vermont 05405
Search for more papers by this authorJeffrey J. MacLean
Spine Bioengineering Lab, School of Engineering, University of Vermont, 33 Colchester Avenue, 201 Perkins Hall, Burlington, Vermont 05405
Search for more papers by this authorAna Barbir
Spine Bioengineering Lab, School of Engineering, University of Vermont, 33 Colchester Avenue, 201 Perkins Hall, Burlington, Vermont 05405
Search for more papers by this authorJustin Stinnett Donnelly
Spine Bioengineering Lab, School of Engineering, University of Vermont, 33 Colchester Avenue, 201 Perkins Hall, Burlington, Vermont 05405
Search for more papers by this authorPeter J. Roughley
Genetics Unit, Shriners Hospital for Children, Montreal, Quebec, Canada
Search for more papers by this authorCorresponding Author
James C. Iatridis
Spine Bioengineering Lab, School of Engineering, University of Vermont, 33 Colchester Avenue, 201 Perkins Hall, Burlington, Vermont 05405
Spine Bioengineering Lab, School of Engineering, University of Vermont, 33 Colchester Avenue, 201 Perkins Hall, Burlington, Vermont 05405; T: 001-802-656-2774; F: 001-802-656-1929.Search for more papers by this authorKarin Wuertz
Spine Bioengineering Lab, School of Engineering, University of Vermont, 33 Colchester Avenue, 201 Perkins Hall, Burlington, Vermont 05405
Spine Research Unit, University Hospital Balgrist, University of Zurich, Zurich, Switzerland
Search for more papers by this authorKarolyn Godburn
Spine Bioengineering Lab, School of Engineering, University of Vermont, 33 Colchester Avenue, 201 Perkins Hall, Burlington, Vermont 05405
Search for more papers by this authorJeffrey J. MacLean
Spine Bioengineering Lab, School of Engineering, University of Vermont, 33 Colchester Avenue, 201 Perkins Hall, Burlington, Vermont 05405
Search for more papers by this authorAna Barbir
Spine Bioengineering Lab, School of Engineering, University of Vermont, 33 Colchester Avenue, 201 Perkins Hall, Burlington, Vermont 05405
Search for more papers by this authorJustin Stinnett Donnelly
Spine Bioengineering Lab, School of Engineering, University of Vermont, 33 Colchester Avenue, 201 Perkins Hall, Burlington, Vermont 05405
Search for more papers by this authorPeter J. Roughley
Genetics Unit, Shriners Hospital for Children, Montreal, Quebec, Canada
Search for more papers by this authorCorresponding Author
James C. Iatridis
Spine Bioengineering Lab, School of Engineering, University of Vermont, 33 Colchester Avenue, 201 Perkins Hall, Burlington, Vermont 05405
Spine Bioengineering Lab, School of Engineering, University of Vermont, 33 Colchester Avenue, 201 Perkins Hall, Burlington, Vermont 05405; T: 001-802-656-2774; F: 001-802-656-1929.Search for more papers by this authorAbstract
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
REFERENCES
- 1 An HS, Anderson PA, Haughton VM, et al. 2004. Introduction: disc degeneration: summary. Spine 29: 2677–2678.
- 2 Adams MA, Roughley PJ. 2006. What is intervertebral disc degeneration, and what causes it? Spine 31: 2151–2161.
- 3 Battie MC, Videman T. 2006. Lumbar disc degeneration: epidemiology and genetics. J Bone Joint Surg [Am] 88 (Suppl 2): 3–9.
- 4 Hadjipavlou AG, Tzermiadianos MN, Bogduk N, et al. 2008. The pathophysiology of disc degeneration: a critical review. J Bone Joint Surg [Br] 90: 1261–1270.
- 5 Setton LA, Chen J. 2006. Mechanobiology of the intervertebral disc and relevance to disc degeneration. J Bone Joint Surg [Am] 88 (Suppl 2): 52–57.
- 6 Stokes IA, Iatridis JC. 2004. Mechanical conditions that accelerate intervertebral disc degeneration: overload versus immobilization. Spine 29: 2724–2732.
- 7 Urban JP, Smith S, Fairbank JC. 2004. Nutrition of the intervertebral disc. Spine 29: 2700–2709.
- 8 Iatridis JC, MacLean JJ, Roughley PJ, et al. 2006. Effects of mechanical loading on intervertebral disc metabolism in vivo. J Bone Joint Surg [Am] 88 (Suppl 2): 41–46.
- 9 Lotz JC, Chin JR. 2000. Intervertebral disc cell death is dependent on the magnitude and duration of spinal loading. Spine 25: 1477–1483.
- 10 Roughley PJ. 2004. Biology of intervertebral disc aging and degeneration: involvement of the extracellular matrix. Spine 29: 2691–2699.
- 11 Gruber HE, Hanley EN Jr. 2002. Observations on morphologic changes in the aging and degenerating human disc: secondary collagen alterations. BMC Musculoskelet Disord 3: 9.
- 12 Mimura M, Panjabi MM, Oxland TR, et al. 1994. Disc degeneration affects the multidirectional flexibility of the lumbar spine. Spine 19: 1371–1380.
- 13 Lotz JC. 2004. Animal models of intervertebral disc degeneration: lessons learned. Spine 29: 2742–2750.
- 14 Court C, Colliou OK, Chin JR, et al. 2001. The effect of static in vivo bending on the murine intervertebral disc. Spine J 1: 239–245.
- 15 Iatridis JC, Mente PL, Stokes IA, et al. 1999. Compression-induced changes in intervertebral disc properties in a rat tail model. Spine 24: 996–1002.
- 16 Lotz JC, Colliou OK, Chin JR, et al. 1998. Compression-induced degeneration of the intervertebral disc: an in vivo mouse model and finite-element study. Spine 23: 2493–2506.
- 17 Hutton WC, Toribatake Y, Elmer WA, et al. 1998. The effect of compressive force applied to the intervertebral disc in vivo. A study of proteoglycans and collagen. Spine 23: 2524–2537.
- 18 MacLean JJ, Lee CR, Grad S, et al. 2003. Effects of immobilization and dynamic compression on intervertebral disc cell gene expression in vivo. Spine 28: 973–981.
- 19
Stinnett-Donnelly J,
MacLean J,
Iatridis J.
2007.
Removable precision device for in-vivo mechanical compression of rat tail intervertebral discs.
J Med Devices
1:
56–61.
10.1115/1.2355692 Google Scholar
- 20 Maclean JJ, Lee CR, Alini M, et al. 2004. Anabolic and catabolic mRNA levels of the intervertebral disc vary with the magnitude and frequency of in vivo dynamic compression. J Orthop Res 22: 1193–1200.
- 21 Maclean JJ, Roughley PJ, Monsey RD, et al. 2008. In vivo intervertebral disc remodeling: kinetics of mRNA expression in response to a single loading event. J Orthop Res 26: 579–588.
- 22 MacLean JJ, Lee CR, Alini M, et al. 2005. The effects of short-term load duration on anabolic and catabolic gene expression in the rat tail intervertebral disc. J Orthop Res 23: 1120–1127.
- 23 Lee CR, Grad S, Maclean JJ, et al. 2005. Effect of mechanical loading on mRNA levels of common endogenous controls in articular chondrocytes and intervertebral disk. Anal Biochem 341: 372–375.
- 24 Farndale RW, Buttle DJ, Barrett AJ. 1986. Improved quantitation and discrimination of sulphated glycosaminoglycans by use of dimethylmethylene blue. Biochim Biophys Acta 883: 173–177.
- 25 Hutton WC, Elmer WA, Boden SD, et al. 1999. The effect of hydrostatic pressure on intervertebral disc metabolism. Spine 24: 1507–1515.
- 26 Hutton WC, Elmer WA, Bryce LM, et al. 2001. Do the intervertebral disc cells respond to different levels of hydrostatic pressure? Clin Biomech (Bristol, Avon) 16: 728–734.
- 27 Ragan PM, Badger AM, Cook M, et al. 1999. Down-regulation of chondrocyte aggrecan and type-II collagen gene expression correlates with increases in static compression magnitude and duration. J Orthop Res 17: 836–842.
- 28 Hsieh AH, Lotz JC. 2003. Prolonged spinal loading induces matrix metalloproteinase-2 activation in intervertebral discs. Spine 28: 1781–1788.
- 29 Pfirrmann CW, Metzdorf A, Elfering A, et al. 2006. Effect of aging and degeneration on disc volume and shape: a quantitative study in asymptomatic volunteers. J Orthop Res 24: 1086–1094.
- 30 Stokes IA, Windisch L. 2006. Vertebral height growth predominates over intervertebral disc height growth in adolescents with scoliosis. Spine 31: 1600–1604.
- 31 O'Connell GD, Vresilovic EJ, Elliott DM. 2007. Comparison of animals used in disc research to human lumbar disc geometry. Spine 32: 328–333.
- 32 Alini M, Eisenstein SM, Ito K, et al. 2008. Are animal models useful for studying human disc disorders/degeneration? Eur Spine J 17: 2–19.
- 33 Erwin WM, Inman RD. 2006. Notochord cells regulate intervertebral disc chondrocyte proteoglycan production and cell proliferation. Spine 31: 1094–1099.
- 34 Hunter CJ, Matyas JR, Duncan NA. 2003. The notochordal cell in the nucleus pulposus: a review in the context of tissue engineering. Tissue Eng 9: 667–677.
- 35 Hayes AJ, Benjamin M, Ralphs JR. 2001. Extracellular matrix in development of the intervertebral disc. Matrix Biol 20: 107–121.
- 36 Hunter CJ, Matyas JR, Duncan NA. 2004. Cytomorphology of notochordal and chondrocytic cells from the nucleus pulposus: a species comparison. J Anat 205: 357–362.
- 37 Grunhagen T, Wilde G, Soukane DM, et al. 2006. Nutrient supply and intervertebral disc metabolism. J Bone Joint Surg [Am] 88 (Suppl 2): 30–35.
- 38 Court C, Chin JR, Liebenberg E, et al. 2007. Biological and mechanical consequences of transient intervertebral disc bending. Eur Spine J 16: 1899–1906.
- 39 Costi JJ, Stokes IA, Gardner-Morse M, et al. 2007. Direct measurement of intervertebral disc maximum shear strain in six degrees of freedom: motions that place disc tissue at risk of injury. J Biomech 40: 2457–2466.