Differential Gene Expression in Anterior and Posterior Annulus Fibrosus

Study Design. Laboratory study. Objective. To evaluate the differential gene expression of cytokines and growth factors in anterior versus posterior annulus fibrosus (AF) intervertebral disc (IVD) specimens. Summary of Background Data. Histological analysis has demonstrated regional differences in vascular and neural ingrowth in the IVD, and similar differences may exist for cytokine and growth factor expression in patients with degenerative disc disease (DDD). Regional expression of these cytokines may also be related to the pain experienced in DDD. Methods. IVD tissue was obtained from patients undergoing anterior lumbar interbody fusion surgery for back pain with radiological evidence of disc degeneration. For a control group, the discs of patients undergoing anterior lumbar discectomy for degenerative scoliosis were obtained as well. The tissue was carefully removed and separated into anterior and posterior AF. After tissue processing, an antibody array was completed to determine expression levels of 42 cytokines and growth factors. Results. Nine discs from 7 patients with DDD and 5 discs from 2 patients with scoliosis were analyzed. In the DDD group, there were 10 cytokines and growth factors with significantly increased expression in the posterior AF versus the anterior AF ([interleukin] IL-4, IL-5, IL-6, M-CSF, MDC, tumor necrosis factor &bgr;, EGF, IGF-1, angiogenin, leptin). In the scoliosis group, only angiogenin and PDGF-BB demonstrated increased expression in the posterior AF. No cytokines or growth factors had increased expression in the anterior AF compared with posterior AF. Conclusion. The posterior AF expresses increased levels of cytokines and growth factors compared with the anterior AF in patients with DDD. This differential expression may be important for targeting treatment of painful IVDs. Level of Evidence: N/A

[1]  Zachary R. Schoepflin,et al.  CCN2 Suppresses Catabolic Effects of Interleukin-1β through α5β1 and αVβ3 Integrins in Nucleus Pulposus Cells , 2014, The Journal of Biological Chemistry.

[2]  Gunnar B. J. Andersson,et al.  Damage accumulation location under cyclic loading in the lumbar disc shifts from inner annulus lamellae to peripheral annulus with increasing disc degeneration. , 2014, Journal of biomechanics.

[3]  M. Adams,et al.  Do intervertebral discs degenerate before they herniate, or after? , 2013, The bone & joint journal.

[4]  T. Albert,et al.  Expression and Relationship of Proinflammatory Chemokine RANTES/CCL5 and Cytokine IL-1&bgr; in Painful Human Intervertebral Discs , 2013, Spine.

[5]  F. Nielsen,et al.  Characterization of miRNA Expression in Human Degenerative Lumbar Disks , 2013, Connective tissue research.

[6]  W. Wu,et al.  The Role of Leptin on the Organization and Expression of Cytoskeleton Elements in Nucleus Pulposus Cells , 2013, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.

[7]  M. Adams,et al.  Annulus Fissures Are Mechanically and Chemically Conducive to the Ingrowth of Nerves and Blood Vessels , 2012, Spine.

[8]  T. Albert,et al.  Substance P Stimulates Production of Inflammatory Cytokines in Human Disc Cells , 2012, Spine.

[9]  Nathaniel T. Hollingsworth,et al.  The Stress and Strain States of the Posterior Annulus Under Flexion , 2012, Spine.

[10]  D. Kletsas,et al.  Exogenous and autocrine growth factors stimulate human intervertebral disc cell proliferation via the ERK and Akt pathways , 2012, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.

[11]  F. Girardi,et al.  Degenerative Scoliosis: A Review , 2011, HSS Journal ®.

[12]  D. Elliott,et al.  Human intervertebral disc internal strain in compression: The effect of disc region, loading position, and degeneration , 2011, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.

[13]  E. Tessitore,et al.  Influence of cytokine inhibitors on concentration and activity of MMP-1 and MMP-3 in disc herniation , 2009, Arthritis research & therapy.

[14]  Joon Ho Wang,et al.  Comparison of growth factor and cytokine expression in patients with degenerated disc disease and herniated nucleus pulposus. , 2009, Clinical biochemistry.

[15]  H. Gruber,et al.  1,25(OH)2-Vitamin D3 Inhibits Proliferation and Decreases Production of Monocyte Chemoattractant Protein-1, Thrombopoietin, VEGF, and Angiogenin by Human Annulus Cells In Vitro , 2008, Spine.

[16]  D. Kletsas,et al.  Growth Factors in Intervertebral Disc Homeostasis , 2008, Connective tissue research.

[17]  Robert J. Moore,et al.  The Natural History of Age-related Disc Degeneration: The Pathology and Sequelae of Tears , 2007, Spine.

[18]  H. Gruber,et al.  Leptin expression by annulus cells in the human intervertebral disc. , 2007, The spine journal : official journal of the North American Spine Society.

[19]  S. Ohtori,et al.  The Degenerated Lumbar Intervertebral Disc is Innervated Primarily by Peptide-Containing Sensory Nerve Fibers in Humans , 2006, Spine.

[20]  P. Roughley,et al.  Tumor Necrosis Factor&agr; Modulates Matrix Production and Catabolism in Nucleus Pulposus Tissue , 2005, Spine.

[21]  Jin soo Park,et al.  Positive feedback loop of interleukin-1beta upregulating production of inflammatory mediators in human intervertebral disc cells in vitro. , 2005, Journal of neurosurgery. Spine.

[22]  A. Freemont,et al.  The role of interleukin-1 in the pathogenesis of human Intervertebral disc degeneration , 2005, Arthritis research & therapy.

[23]  S. Goldring,et al.  The role of cytokines in cartilage matrix degeneration in osteoarthritis. , 2004, Clinical orthopaedics and related research.

[24]  B. Peng,et al.  [The pathogenesis of discogenic low back pain]. , 2004, Zhonghua wai ke za zhi [Chinese journal of surgery].

[25]  Clifford B Tribus,et al.  Degenerative Lumbar Scoliosis: Evaluation and Management , 2003, The Journal of the American Academy of Orthopaedic Surgeons.

[26]  J. Melrose,et al.  Induction of matrix metalloproteinase-2 and -3 activity in ovine nucleus pulposus cells grown in three-dimensional agarose gel culture by interleukin-1β: a potential pathway of disc degeneration , 2003, European Spine Journal.

[27]  S. Bruehlmann,et al.  Regional variations in the cellular matrix of the annulus fibrosus of the intervertebral disc , 2002, Journal of anatomy.

[28]  A. Freemont,et al.  Nerve growth factor expression and innervation of the painful intervertebral disc , 2002, The Journal of pathology.

[29]  S. Jang,et al.  mRNA Expression of Cytokines and Chemokines in Herniated Lumbar Intervertebral Discs , 2002, Spine.

[30]  J. Fitzpatrick,et al.  Intervertebral discs which cause low back pain secrete high levels of proinflammatory mediators. , 2002, The Journal of bone and joint surgery. British volume.

[31]  S. Roberts,et al.  Matrix Metalloproteinases in the Human Intervertebral Disc: Role in Disc Degeneration and Scoliosis , 1997, Spine.

[32]  M. Jayson,et al.  Nerve ingrowth into diseased intervertebral disc in chronic back pain , 1997, The Lancet.

[33]  D S McNally,et al.  'Stress' distributions inside intervertebral discs. The effects of age and degeneration. , 1996, The Journal of bone and joint surgery. British volume.

[34]  Michael A. Adams,et al.  'Stress' distributions inside intervertebral discs , 1996 .

[35]  E. Karaharju,et al.  Prevalence, Morphology, and Topography of Blood Vessels in Herniated Disc Tissue: A Comparative Immunocytochemical Study , 1996, Spine.

[36]  James D. Kang,et al.  Herniated Lumbar Intervertebral Discs Spontaneously Produce Matrix Metalloproteinases, Nitric Oxide, Interleukin-6, and Prostaglandin E2 , 1996, Spine.

[37]  T. Kakiuchi,et al.  Inflammatory Cytokines in the Herniated Disc of the Lumbar Spine , 1996, Spine.

[38]  S. Roberts,et al.  Mechanoreceptors in Intervertebral Discs: Morphology, Distribution, and Neuropeptides , 1995, Spine.

[39]  James D. Kang,et al.  Herniated Cervical Intervertebral Discs Spontaneously Produce Matrix Metalloproteinases, Nitric Oxide, Interleukin‐6, and Prostaglandin E2 , 1995, Spine.

[40]  F. Cunha,et al.  Cytokine‐mediated inflammatory hyperalgesia limited by interleukin‐4 , 1995, British journal of pharmacology.

[41]  J. Urban,et al.  The chondrocyte: a cell under pressure. , 1994, British journal of rheumatology.

[42]  N. Obuchowski,et al.  Magnetic Resonance Imaging of the lumbar spine in people without back pain , 2017, AL-QADISIYAH MEDICAL JOURNAL.

[43]  S. Roberts,et al.  Neuropeptides in the human intervertebral disc , 1994, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.

[44]  T. Kikuchi,et al.  The role of interleukin-1 on proteoglycan metabolism of rabbit annulus fibrosus cells cultured in vitro. , 1988, Spine.

[45]  I. Shapiro,et al.  Role of cytokines in intervertebral disc degeneration: pain and disc content , 2014, Nature Reviews Rheumatology.

[46]  A. Baker Abnormal Magnetic-Resonance Scans of the Lumbar Spine in Asymptomatic Subjects. A Prospective Investigation , 2014 .

[47]  A. Sharma,et al.  Light Microscopic Study of The Lumbar Intervertebral Disc Showing Inherent Difference Between Anterior & Posterior Annulus Fibrosus - A Risk Factor For Posterior Disc Herniation , 2011 .

[48]  L. Kauppila,et al.  Ingrowth of blood vessels in disc degeneration. Angiographic and histological studies of cadaveric spines. , 1995, The Journal of bone and joint surgery. American volume.

[49]  C HIRSCH,et al.  Studies on structural changes in the lumbar annulus fibrosus. , 1952, Acta orthopaedica Scandinavica.