The Journal of Bone and Joint Surgery (American). 2006;88:52-57.
doi:10.2106/JBJS.F.00001
© 2006 The Journal of Bone and Joint Surgery, Inc.
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Letters to the Editor: Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when Letters to the Editor are posted
Right arrow Alert me if a correction is posted
Services
Right arrow E-mail this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My File Cabinet
Right arrow Download to citation manager
Right arrow Rights and Permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Setton, L. A.
Right arrow Articles by Chen, J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Setton, L. A.
Right arrow Articles by Chen, J.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us   Add to Facebook   Add to Technorati   Add to Twitter  
What's this?

Mechanobiology of the Intervertebral Disc and Relevance to Disc Degeneration

Lori A. Setton, PhD and Jun Chen, PhD

Corresponding author:
Lori A. Setton, PhD
Cartilage Mechanics and Tissue Engineering Laboratory, Department of Biomedical Engineering, Duke University, 136 Hudson Hall, Box 90281, Durham, NC 27708.
E-mail address: setton{at}duke.edu

NOTE: The authors are grateful to Drs. William J. Richardson, Chris L. Gilchrist, and Maureen L. Upton for their contributions.

In support of their research for or preparation of this manuscript, one or more of the authors received grants or outside funding from the National Institutes of Health (AR047442 and AR050245). None of the authors received payments or other benefits or a commitment or agreement to provide such benefits from a commercial entity. No commercial entity paid or directed, or agreed to pay or direct, any benefits to any research fund, foundation, educational institution, or other charitable or nonprofit organization with which the authors are affiliated or associated.

Mechanical loading of the intervertebral disc may contribute to disc degeneration by initiating degeneration or by regulating cell-mediated remodeling events that occur in response to the mechanical stimuli of daily activity. This article is a review of the current knowledge of the role of mechanical stimuli in regulating intervertebral disc cellular responses to loading and the cellular changes that occur with degeneration.

Intervertebral disc cells exhibit diverse biologic responses to mechanical stimuli, depending on the loading type, magnitude, duration, and anatomic zone of cell origin. The innermost cells respond to low-to-moderate magnitudes of static compression, osmotic pressure, or hydrostatic pressure with increases in anabolic cell responses. Higher magnitudes of loading may give rise to catabolic responses marked by elevated protease gene or protein expression or activity. The key regulators of these mechanobiologic responses for intervertebral disc cells will be the micromechanical stimuli experienced at the cellular level, which are predicted to differ from that measured for the extracellular matrix. Large hydrostatic pressures, but little volume change, are predicted to occur for cells of the nucleus pulposus during compression, while the highly oriented cells of the anulus fibrosus may experience deformations in tension or compression during matrix deformations. In general, the pattern of biologic response to applied loads suggests that the cells of the nucleus pulposus and inner portion of the anulus fibrosus experience comparable micromechanical stimuli in situ and may respond more similarly than cells of the outer portion of the anulus fibrosus. Changes in these features with degeneration are critically understudied, particularly degeneration-associated changes in cell-level mechanical stimuli and the associated mechanobiology.

Little is known of the mechanisms that regulate cellular responses to intervertebral mechanobiology, nor is much known with regard to the precise mechanical stimuli experienced by cells during loading. Mechanical factors appear to regulate responses of the intervertebral disc cells through mechanisms involving intracellular Ca2+ transients and cytoskeletal remodeling that may regulate downstream effects such as gene expression and posttranslational biosynthesis. Future studies should address the broader biologic responses to mechanical stimuli in intervertebral disc mechanobiology, the involved signaling mechanisms, and the apparently important interactions among mechanical factors, genetic factors, cytokines, and inflammatory mediators that may be critical in the regulation of intervertebral disc degeneration.


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Facebook Facebook   Add to Technorati Technorati   Add to Twitter Twitter    What's this?


This article has been cited by other articles:


Home page
 J. Biol. Chem.Home page
A. Hiyama, S. Gajghate, D. Sakai, J. Mochida, I. M. Shapiro, and M. V. Risbud
Activation of TonEBP by Calcium Controls {beta}1,3-Glucuronosyltransferase-I Expression, a Key Regulator of Glycosaminoglycan Synthesis in Cells of the Intervertebral Disc
J. Biol. Chem., April 10, 2009; 284(15): 9824 - 9834.
[Abstract] [Full Text] [PDF]

Home page
 J. Histochem. Cytochem.Home page
V. Y.L. Leung, W. C.W. Chan, S.-C. Hung, K. M.C. Cheung, and D. Chan
Matrix Remodeling During Intervertebral Disc Growth and Degeneration Detected by Multichromatic FAST Staining
J. Histochem. Cytochem., March 1, 2009; 57(3): 249 - 256.
[Abstract] [Full Text] [PDF]

Home page
 Rheumatology (Oxford)Home page
A. J. Freemont
The cellular pathobiology of the degenerate intervertebral disc and discogenic back pain
Rheumatology, January 1, 2009; 48(1): 5 - 10.
[Abstract] [Full Text] [PDF]

Home page
 JBJSHome page
P. O. Newton, V. V. Upasani, C. L. Farnsworth, R. Oka, R. C. Chambers, J. Dwek, J. R. Kim, A. Perry, and A. T. Mahar
Spinal Growth Modulation with Use of a Tether in an Immature Porcine Model
J. Bone Joint Surg. Am., December 1, 2008; 90(12): 2695 - 2706.
[Abstract] [Full Text] [PDF]