Relationship Between Inflammatory Stimulation and Cell Biomechanics in Intervertebral Disc Degeneration

Intervertebral disc (IVD) degeneration (DD) affects over 40% of adults, is a leading cause of disability and costs over $100 billion in economic burden annually. DD is a multifactorial process ultimately leading to tissue breakdown and loss of functionality. DD is associated with increased levels of inflammatory cytokines within the disc and the catabolic effect of inflammatory stimulation on disc biology has been well studied. As part of its physiological functioning the disc experiences mechanical, hydrostatic, and osmotic stimuli. Cells within the disc are mechanosensitive to these signals, where hyper physiological or damaging signals can perpetuate degenerative effects in the disc. Despite the known contributions of inflammatory stimulation and biomechanics to DD individually, their interaction in the context of the IVD is still not well understood. The objective of this thesis is to examine the role of inflammatory stimulation on cellular biophysical properties in the disc, subsequent implications at the tissue level, and contributions to DD. Here the cell cytoskeleton and actomyosin contractility are identified as key regulators of the response of cellular properties to inflammation. Actomyosin contractility is further identified as a regulator of well-known biological responses to inflammatory stimulation within the disc including ECM catabolism and altered tissue mechanics. Altered cellular biophysical properties observed in clinical human DD samples indicate the inflammatory milieu present in DD drive changes in cellular mechanics. Increasing actomyosin contractility is shown to be effective in mitigating the effects of inflammation on cellular biophysical properties and subsequent degenerative effects highlighting its potential as a therapeutic for the treatment of DD.

Year	Entry
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2014	Bajpayee AG, Wong CR, Bawendi MG, Frank EH, Grodzinsky AJ. Avidin as a model for charge driven transport into cartilage and drug delivery for treating early stage post-traumatic osteoarthritis. Biomaterials. January 2014;35(1):538-549.
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Year

Entry

1999

Guilak F, Ting-Beall HP, Baer AE, Trickey WR, Erickson GR, Setton LA. Viscoelastic properties of intervertebral disc cells: identification of two biomechanically distinct cell populations. Spine. December 1, 1999;24(23):2475-2483.

2001

Pfirrmann CWA, Metzdorf A, Zanetti M, Hodler J, Boos N. Magnetic resonance classification of lumbar intervertebral disc degeneration. Spine. September 1, 2001;26(17):1873-1878.

1995

Ohshima H, Urban JPG, Bergel DH. Effect of static load on matrix synthesis rates in the intervertebral disc measured in vitro by a new perfusion technique. J Orthop Res. January 1995;13(1):22-29.

1988

Urban JPG, McMullin JF. Swelling pressure of the lumbar intervertebral discs influence of age, spinal level, composition, and degeneration. Spine. February 1988;13(2):179-187.

2014

Bajpayee AG, Wong CR, Bawendi MG, Frank EH, Grodzinsky AJ. Avidin as a model for charge driven transport into cartilage and drug delivery for treating early stage post-traumatic osteoarthritis. Biomaterials. January 2014;35(1):538-549.