Intervertebral disc degeneration: biological and biomechanical factors

There has been significant progress over the past two decades in the surgical treatment of spinal disorders, including advances in spinal instrumentation, minimally invasive spine surgery, biomaterials, and artificial disc replacement. Although improvements in surgical treatments are on track, basic science research on the pathogenesis of intervertebral disc (IVD) degeneration and the mechanism of pain is nascent. A better understanding of the pathogenesis of IVD degeneration will culminate in greater advances in treatment and improve patient selection and indications for emerging techniques and procedures. In this article, we review the relevant literature on biological and biomechanical research, including our own recent publications.

[1]  V. Haughton,et al.  Measuring diffusion of solutes into intervertebral disks with MR imaging and paramagnetic contrast medium. , 1998, AJNR. American journal of neuroradiology.

[2]  E. Thonar,et al.  Osteogenic Protein-1 Injection Into a Degenerated Disc Induces the Restoration of Disc Height and Structural Changes in the Rabbit Anular Puncture Model , 2006, Spine.

[3]  L. Autilio‐Gambetti,et al.  Binding of Bodian's Silver and Monoclonal Antibodies to Defined Regions of Human Neurofilament Subunits: Bodian's Silver Reacts with a Highly Charged Unique Domain of Neurofilaments , 1986, Journal of neurochemistry.

[4]  S. Kikuchi,et al.  In vivo intradiscal pressure measurement in healthy individuals and in patients with ongoing back problems. , 1999, Spine.

[5]  J. Mochida,et al.  Reinsertion of stimulated nucleus pulposus cells retards intervertebral disc degeneration: An in vitro and in vivo experimental study , 2000, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.

[6]  J. P. Thompson,et al.  Preliminary Evaluation of a Scheme for Grading the Gross Morphology of the Human Intervertebral Disc , 1990, Spine.

[7]  E. Thonar,et al.  Osteogenic protein-1 is most effective in stimulating nucleus pulposus and annulus fibrosus cells to repair their matrix after chondroitinase ABC-induced in vitro chemonucleolysis. , 2005, The spine journal : official journal of the North American Spine Society.

[8]  Thomas R Oxland,et al.  Degenerative mechanics of the lumbar spine. , 2004, The spine journal : official journal of the North American Spine Society.

[9]  L G Gilbertson,et al.  Modulation of the biologic activity of the rabbit intervertebral disc by gene therapy: an in vivo study of adenovirus-mediated transfer of the human transforming growth factor beta 1 encoding gene. , 1999, Spine.

[10]  A. Freemont,et al.  Matrix Metalloproteinases: The Clue to Intervertebral Disc Degeneration? , 1998, Spine.

[11]  J. Mochida.  New strategies for disc repair: novel preclinical trials , 2005, Journal of orthopaedic science : official journal of the Japanese Orthopaedic Association.

[12]  H. Farfan,et al.  Mechanical disorders of the low back , 1973 .

[13]  K. Hirabayashi,et al.  Neutral proteinases in human intervertebral disc. Role in degeneration and probable origin. , 1993, Spine.

[14]  Howard S. An,et al.  The relationship between facet joint osteoarthritis and disc degeneration of the lumbar spine: an MRI study , 1999, European Spine Journal.

[15]  P. Khalsa,et al.  Human lumbar facet joint capsule strains: I. During physiological motions. , 2004, The spine journal : official journal of the North American Spine Society.

[16]  H E Gruber,et al.  Human intervertebral disc cells from the annulus: three-dimensional culture in agarose or alginate and responsiveness to TGF-beta1. , 1997, Experimental cell research.

[17]  T. Albert,et al.  Cellular Therapy for Disc Degeneration , 2005, Spine.

[18]  E. Thonar,et al.  Biological Repair of Intervertebral Disc , 2003, Spine.

[19]  H. An,et al.  Growth factors and the intervertebral disc. , 2004, The spine journal : official journal of the North American Spine Society.

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

[21]  T P Hedman,et al.  A new transducer for facet force measurement in the lumbar spine: benchmark and in vitro test results. , 1992, Journal of biomechanics.

[22]  V. Haughton,et al.  The Stiffness of Lumbar Spinal Motion Segments With a High‐Intensity Zone in the Anulus Fibrosus , 1998, Spine.

[23]  P Kurowski,et al.  The Relationship of Degeneration of the Intervertebral Disc to Mechanical Loading Conditions on Lumbar Vertebrae , 1986, Spine.

[24]  G R Fernie,et al.  Mechanical Response of the Lumbar Spine to Seated Postural Loads , 1997, Spine.

[25]  King H. Yang,et al.  Mechanism of facet load transmission as a hypothesis for low-back pain. , 1984, Spine.

[26]  W C Hutton,et al.  The effect of posture on the role of the apophysial joints in resisting intervertebral compressive forces. , 1980, The Journal of bone and joint surgery. British volume.

[27]  Tong-Chuan He,et al.  Potential Use of Sox9 Gene Therapy for Intervertebral Degenerative Disc Disease , 2003, Spine.

[28]  S D Gertzbein,et al.  Centrode Patterns and Segmental Instability in Degenerative Disc Disease , 1985, Spine.

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

[30]  V. Haughton,et al.  Effect of axial loading on neural foramina and nerve roots in the lumbar spine. , 1990, Radiology.

[31]  J C Fairbank,et al.  Electrochemical Measurement of Transport Into Scoliotic Intervertebral Discs In Vivo Using Nitrous Oxide as a Tracer , 2001, Spine.

[32]  P. Dreyfuss,et al.  Low back pain and the zygapophysial (facet) joints. , 1996, Archives of physical medicine and rehabilitation.

[33]  W. Richter,et al.  Release of active and depot GDF-5 after adenovirus-mediated overexpression stimulates rabbit and human intervertebral disc cells , 2004, Journal of Molecular Medicine.

[34]  M. Adams,et al.  The Relevance of Torsion to the Mechanical Derangement of the Lumbar Spine , 1981, Spine.

[35]  T P Andriacchi,et al.  Study on effect of graded facetectomy on change in lumbar motion segment torsional flexibility using three-dimensional continuum contact representation for facet joints. , 1999, Journal of biomechanical engineering.

[36]  M. Panjabi,et al.  Biomechanical Evaluation of Lumbar Spinal Stability After Graded Facetectomies , 1990, Spine.

[37]  P. Khalsa,et al.  Human lumbar facet joint capsule strains: II. Alteration of strains subsequent to anterior interbody fixation. , 2004, The spine journal : official journal of the North American Spine Society.

[38]  L. Riley,et al.  Effect of degeneration of the intervertebral disk on the process of diffusion. , 1997, AJNR. American journal of neuroradiology.

[39]  Koichi Masuda,et al.  A Novel Rabbit Model of Mild, Reproducible Disc Degeneration by an Anulus Needle Puncture: Correlation Between the Degree of Disc Injury and Radiological and Histological Appearances of Disc Degeneration , 2005, Spine.

[40]  R. Yeasting,et al.  The Quantitative Anatomy of the Thoracic Facet and the Posterior Projection of Its Inferior Facet , 1997, Spine.

[41]  E. Thonar,et al.  Recombinant osteogenic protein‐1 upregulates extracellular matrix metabolism by rabbit annulus fibrosus and nucleus pulposus cells cultured in alginate beads , 2003, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.

[42]  P. O'leary.  Lumbar Spine Instability , 1992 .

[43]  W. Horton,et al.  Which Disc as Visualized by Magnetic Resonance Imaging Is Actually a Source of Pain?: A Correlation between Magnetic Resonance Imaging and Discography , 1992, Spine.

[44]  H. Baba,et al.  Herniation of Cervical Intervertebral Disc: Immunohistochemical Examination and Measurement of Nitric Oxide Production , 2001, Spine.

[45]  Baxter P Rogers,et al.  Application of image registration to measurement of intervertebral rotation in the lumbar spine , 2002, Magnetic resonance in medicine.

[46]  M. Zimmerman,et al.  Development of a Prosthetic Intervertebral Disc , 1991, Spine.

[47]  W C Hutton,et al.  Cadaver lumbar intervertebral joints. , 1980, Spine.

[48]  W. Hutton,et al.  Inhibition of proteoglycan and type II collagen synthesis of disc nucleus cells by nicotine. , 2003, Journal of neurosurgery.

[49]  S Gracovetsky,et al.  The Nature of Instability , 1984, Spine.

[50]  V. Haughton,et al.  Tears of the anulus fibrosus: correlation between MR and pathologic findings in cadavers. , 1988, AJNR. American journal of neuroradiology.

[51]  W C Hutton,et al.  Disc space narrowing and the lumbar facet joints. , 1984, The Journal of bone and joint surgery. British volume.

[52]  N. Boos,et al.  2002 SSE Award Competition in Basic Science: Expression of major matrix metalloproteinases is associated with intervertebral disc degradation and resorption , 2002, European Spine Journal.

[53]  A Shirazi-Adl,et al.  Finite Element Study of Nutrient Diffusion in the Human Intervertebral Disc , 2003, Spine.

[54]  D. Polly,et al.  Surgical Treatment for the Painful Motion Segment: Matching Technology With the Indications: Posterior Lumbar Fusion , 2005, Spine.

[55]  M. Barry,et al.  Facet joint hypertrophy: The cross-sectional area of the superior articular process of L4 and L5 , 2005, European Spine Journal.

[56]  M. Zlatkin,et al.  In vivo and ex vivo magnetic resonance imaging evaluation of early disc degeneration with histopathologic correlation. , 1991, Spine.

[57]  V. Haughton,et al.  Neural foraminal ligaments of the lumbar spine: appearance at CT and MR imaging. , 1992, Radiology.

[58]  Lars G. Gilbertson,et al.  Gene Transfer of the Catabolic Inhibitor TIMP-1 Increases Measured Proteoglycans in Cells from Degenerated Human Intervertebral Discs , 2003, Spine.

[59]  M. Schendel,et al.  Biomechanical Analysis of Facet and Graft Loading in a Smith‐Robinson Type Cervical Spine Model , 1994, Spine.

[60]  K. Olmarker,et al.  Tumor necrosis factor alpha and nucleus-pulposus-induced nerve root injury. , 1998, Spine.

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

[62]  N. Langrana,et al.  Modeling of facet articulation as a nonlinear moving contact problem: sensitivity study on lumbar facet response. , 1998, Journal of biomechanical engineering.

[63]  Scott W Wolfe,et al.  Carpal bone postures and motions are abnormal in both wrists of patients with unilateral scapholunate interosseous ligament tears. , 2003, The Journal of hand surgery.

[64]  R. Yeasting,et al.  Quantitative anatomy of the cervical facet and the posterior projection of its inferior facet. , 1997, Journal of spinal disorders.

[65]  S. Gracovetsky,et al.  A Database for Estimating Normal Spinal Motion Derived From Noninvasive Measurements , 1995, Spine.

[66]  H. Iwata,et al.  The Involvement of Matrix Metalloproteinases and Inflammation in Lumbar Disc Herniation , 1998, Spine.

[67]  E. Thonar,et al.  Osteogenic protein-1 enhances matrix replenishment by intervertebral disc cells previously exposed to interleukin-1. , 2002, Spine.

[68]  W. Hutton,et al.  The Effect of Bone Morphogenetic Protein-2 on Rat Intervertebral Disc Cells in Vitro , 2003, Spine.

[69]  A. Patwardhan,et al.  Load-bearing characteristics of lumbar facets in normal and surgically altered spinal segments. , 1983, Spine.

[70]  A. Freemont,et al.  Localization of degradative enzymes and their inhibitors in the degenerate human intervertebral disc , 2004, The Journal of pathology.

[71]  D. W. Bühler,et al.  Facet joint remodeling in degenerative spondylolisthesis: an investigation of joint orientation and tropism , 1998, European Spine Journal.

[72]  S. Moon,et al.  Bone Morphogenetic Protein-2 Facilitates Expression of Chondrogenic, not Osteogenic, Phenotype of Human Intervertebral Disc Cells , 2003, Spine.

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

[74]  藤田 享介.  Neutral proteinases in human intervertebral disc : role in degeneration and probable origin , 1994 .

[75]  T. King,et al.  Primary instability of lumbar vertebrae as a common cause of low back pain. , 1957, The Journal of bone and joint surgery. British volume.

[76]  K. Yonenobu,et al.  Mechanisms of Age-Related Decline in Insulin-Like Growth Factor-I Dependent Proteoglycan Synthesis in Rat Intervertebral Disc Cells , 2001, Spine.

[77]  H. Horner,et al.  2001 Volvo Award Winner in Basic Science Studies: Effect of Nutrient Supply on the Viability of Cells From the Nucleus Pulposus of the Intervertebral Disc , 2001, Spine.

[78]  K. Olmarker,et al.  Tumor Necrosis Factor α and Nucleus‐Pulposus‐Induced Nerve Root Injury , 1998 .

[79]  P. Roughley,et al.  Aggrecan degradation in human intervertebral disc and articular cartilage. , 1997, The Biochemical journal.

[80]  T. Kikuchi,et al.  Matrix metalloproteinase-3 production by human degenerated intervertebral disc. , 1997, Journal of spinal disorders.

[81]  M M Panjabi,et al.  A technique for measurement and description of three-dimensional six degree-of-freedom motion of a body joint with an application to the human spine. , 1981, Journal of biomechanics.

[82]  S. T. Yoon,et al.  Molecular therapy of the intervertebral disc , 2006, European Spine Journal.

[83]  A Shirazi-Adl,et al.  Mechanical Response of a Lumbar Motion Segment in Axial Torque Alone and Combined with Compression , 1986, Spine.

[84]  J W Frymoyer,et al.  Segmental Motion and Instability , 1987, Spine.

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

[86]  C. Peter Winlove,et al.  Oxygen and Lactate Concentrations Measured in Vivo in the Intervertebral Discs of Patients With Scoliosis and Back Pain , 1998, Spine.

[87]  B. Caterson,et al.  Matrix Metalloproteinases And Aggrecanase: Their Role in Disorders of the Human Intervertebral Disc , 2000, Spine.

[88]  Albert I. King,et al.  Structural Considerations of the Human Vertebral Column Under +Gz Impact Acceleration , 1972 .

[89]  H. An,et al.  Orientation and Osteoarthritis of the Lumbar Facet Joint , 2001, Clinical orthopaedics and related research.

[90]  B. Vernon‐roberts,et al.  Osteoarthrosis of the facet joints resulting from anular rim lesions in sheep lumbar discs. , 1999, Spine.

[91]  A. Nachemson.  Lumbar Spine Instability: A Critical Update and Symposium Summary , 1985, Spine.

[92]  H. An,et al.  Growth Factors and Treatment of Intervertebral Disc Degeneration , 2004, Spine.

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

[94]  D G Wilder,et al.  Spine radiographs in patients with low-back pain. An epidemiological study in men. , 1984, The Journal of bone and joint surgery. American volume.

[95]  S. Papson,et al.  “Model” , 1981 .

[96]  J. Cassidy,et al.  Radiologic Diagnosis of Degenerative Lumbar Spinal Instability , 1985, Spine.

[97]  S. Boden.  Biology of lumbar spine fusion and use of bone graft substitutes: present, future, and next generation. , 2000, Tissue engineering.

[98]  M. Panjabi,et al.  Articular Facets of the Human Spine Quantitative Three‐Dimensional Anatomy , 1993, Spine.

[99]  V. Haughton,et al.  A Noninvasive, Three‐Dimensional Spinal Motion Analysis Method , 1997, Spine.

[100]  A. Rohlmann,et al.  Influence of graded facetectomy and laminectomy on spinal biomechanics , 2003, European Spine Journal.

[101]  T. C. Howard,et al.  Roentgenographic Evaluation of Lumbar Spine Flexion‐Extension in Asymptomatic Individuals , 1989, Spine.

[102]  S Holm,et al.  Nutrition of the intervertebral disk. An in vivo study of solute transport. , 1977, Clinical orthopaedics and related research.

[103]  J. Fitzpatrick,et al.  Human Nucleus Pulposis Can Respond to a Pro-inflammatory Stimulus , 2003, Spine.

[104]  Simon X. Yang,et al.  Relationship between pain and vertebral motion in chronic low-back pain subjects. , 2002, Clinical biomechanics.

[105]  R. R. Cooper.  Mechanical Disorders of the Low Back , 1974 .

[106]  J L Lewis,et al.  Experimental measurement of ligament force, facet force, and segment motion in the human lumbar spine. , 1993, Journal of biomechanics.

[107]  M M Panjabi,et al.  Thoracic Human Vertebrae Quantitative Three‐Dimensional Anatomy , 1991, Spine.

[108]  J A Buckwalter,et al.  Aging and degeneration of the human intervertebral disc. , 1995, Spine.

[109]  H. Farfan,et al.  The effects of torsion on the lumbar intervertebral joints: the role of torsion in the production of disc degeneration. , 1970, The Journal of bone and joint surgery. American volume.

[110]  G. Andersson,et al.  Discs Degenerate Before Facets , 1990, Spine.

[111]  J. Lotz,et al.  In Vivo Growth Factor Treatment of Degenerated Intervertebral Discs , 2004, Spine.

[112]  O. Tervonen,et al.  Correlation of diffusion in lumbar intervertebral disks with occlusion of lumbar arteries: a study in adult volunteers. , 2001, Radiology.

[113]  W. J. Oakes,et al.  Surgical experience in 130 pediatric patients with Chiari I malformations. , 2003, Journal of neurosurgery.

[114]  M M Panjabi,et al.  Human Lumbar Vertebrae: Quantitative Three-Dimensional Anatomy , 1992, Spine.

[115]  K. Yudoh,et al.  Autocrine/paracrine mechanism of insulin‐like growth factor‐1 secretion, and the effect of insulin‐like growth factor‐1 on proteoglycan synthesis in bovine intervertebral discs , 1996, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.

[116]  M. Panjabi,et al.  Facet Joint Kinematics and Injury Mechanisms During Simulated Whiplash , 2004, Spine.

[117]  Eric P. Lorenz,et al.  Three-Dimensional In Vivo Measurement of Lumbar Spine Segmental Motion , 2006, Spine.

[118]  T. Nishida.  Kinetics of tissue and serum matrix metalloproteinase-3 and tissue inhibitor of metalloproteinases-1 in intervertebral disc degeneration and disc herniation. , 1999, The Kurume medical journal.

[119]  J. Mort,et al.  Identification of human intervertebral disc stromelysin and its involvement in matrix degradation , 1991, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.

[120]  N. Boos,et al.  Expression and Distribution of Tumor Necrosis Factor Alpha in Human Lumbar Intervertebral Discs: A Study in Surgical Specimen and Autopsy Controls , 2005, Spine.

[121]  M. Modic,et al.  Imaging of degenerative disk disease. , 1988, Radiology.

[122]  A Shirazi-Adl,et al.  Biomechanics of the Lumbar Spine in Sagittal/Lateral Moments , 1994, Spine.

[123]  W. Hutton,et al.  ISSLS Prize Winner: LMP-1 Upregulates Intervertebral Disc Cell Production of Proteoglycans and BMPs In Vitro and In Vivo , 2004, Spine.

[124]  V. Goel,et al.  Load-Sharing Between Anterior and Posterior Elements in a Lumbar Motion Segment Implanted With an Artificial Disc , 2001, Spine.

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

[126]  M. Pearcy,et al.  Three-Dimensional X-ray Analysis of Normal Movement in the Lumbar Spine , 1984, Spine.

[127]  M. Panjabi,et al.  Effects of Disc Injury on Mechanical Behavior of the Human Spine , 1984, Spine.

[128]  D. Grob,et al.  Clinical Validation of Functional Flexion/Extension Radiographs of the Cervical Spine , 1993, Spine.

[129]  C. Pellengahr,et al.  Influence of facet joint angles and asymmetric disk collapse on degenerative olisthesis of the cervical spine. , 2000, Orthopedics.

[130]  J. Mochida,et al.  Percutaneous Reinsertion of the Nucleus Pulposus: An Experimental Study , 1998, Spine.

[131]  G B Andersson,et al.  The Effect of Disc Degeneration and Facet Joint Osteoarthritis on the Segmental Flexibility of the Lumbar Spine , 2000, Spine.

[132]  E. Thonar,et al.  Intradiscal Administration of Osteogenic Protein-1 Increases Intervertebral Disc Height and Proteoglycan Content in the Nucleus Pulposus in Normal Adolescent Rabbits , 2005, Spine.

[133]  W. Hutton,et al.  Disc Chondrocyte Transplantation in a Canine Model: A Treatment for Degenerated or Damaged Intervertebral Disc , 2003, Spine.

[134]  M. Adams,et al.  The Mechanical Function of the Lumbar Apophyseal Joints , 1983, Spine.

[135]  E. Thonar,et al.  Changes in mRNA and Protein Levels of Proteoglycans of the Anulus Fibrosus and Nucleus Pulposus During Intervertebral Disc Degeneration , 2002, Spine.

[136]  V. Haughton,et al.  Flexibility of lumbar spinal motion segments correlated to type of tears in the annulus fibrosus. , 2000, Journal of neurosurgery.

[137]  R. Myers,et al.  Exogenous Tumor Necrosis Factor-Alpha Mimics Nucleus Pulposus-Induced Neuropathology: Molecular, Histologic, and Behavioral Comparisons in Rats , 2000, Spine.

[138]  M M Panjabi,et al.  Mechanical behavior of the human lumbar and lumbosacral spine as shown by three-dimensional load-displacement curves. , 1994, The Journal of bone and joint surgery. American volume.

[139]  T. Haher,et al.  The Role of the Lumbar Facet Joints in Spinal Stability: Identification of Alternative Paths of Loading , 1994, Spine.

[140]  H. An,et al.  Biomechanical Evaluation of Contemporary Posterior Spinal Internal Fixation Configurations in an Unstable Burst-fracture Calf Spine Model: Special References of Hook Configurations and Pedicle Screws , 2004, Spine.

[141]  G. P. Pal,et al.  The orientation of the articular facets of the zygapophyseal joints at the cervical and upper thoracic region , 2001, Journal of anatomy.

[142]  V. Haughton,et al.  Measuring the axial rotation of lumbar vertebrae in vivo with MR imaging. , 2002, AJNR. American journal of neuroradiology.

[143]  M. Adams,et al.  The Resistance to Flexion of the Lumbar Intervertebral Joint , 1980, Spine.

[144]  H. Farfan,et al.  Instability of the lumbar spine. , 1982, Clinical orthopaedics and related research.

[145]  M. Aebi,et al.  A synthetic peptide of link protein stimulates the biosynthesis of collagens II, IX and proteoglycan by cells of the intervertebral disc , 2003, Journal of cellular biochemistry.

[146]  H E Gruber,et al.  Analysis of Aging and Degeneration of the Human Intervertebral Disc: Comparison of Surgical Specimens With Normal Controls , 1998, Spine.

[147]  J. P. Thompson,et al.  Stimulation of Mature Canine Intervertebral Disc by Growth Factors , 1991, Spine.

[148]  H. An,et al.  The relationship between disc degeneration, facet joint osteoarthritis, and stability of the degenerative lumbar spine. , 2000, Journal of spinal disorders.

[149]  Adams Ma,et al.  The relevance of torsion to the mechanical derangement of the lumbar spine. , 1981 .

[150]  M H Pope,et al.  Biomechanical Definitions of Spinal Instability , 1985, Spine.

[151]  S. Peleg,et al.  Facet Orientation in the Thoracolumbar Spine: Three-dimensional Anatomic and Biomechanical Analysis , 2004, Spine.

[152]  H. Gruber,et al.  Anti-Apoptotic Effects of IGF-1 and PDGF on Human Intervertebral Disc Cells In Vitro , 2000, Spine.

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

[154]  M. Pearcy.  Stereo radiography of lumbar spine motion. , 1985, Acta orthopaedica Scandinavica. Supplementum.