Skip to main content

Advertisement

SpringerLink
Log in

Recent advances in annular pathobiology provide insights into rim-lesion mediated intervertebral disc degeneration and potential new approaches to annular repair strategies

  • Review
  • Published:
European Spine Journal Aims and scope Submit manuscript

Abstract

The objective of this study was to assess the impact of a landmark annular lesion model on our understanding of the etiopathogenesis of IVD degeneration and to appraise current IVD repairative strategies. A number of studies have utilised the Osti sheep model since its development in 1990. The experimental questions posed at that time are covered in this review, as are significant recent advances in annular repair strategies. The ovine model has provided important spatial and temporal insights into the longitudinal development of annular lesions and how they impact on other discal and paradiscal components such as the NP, cartilaginous end plates, zygapophyseal joints and vertebral bone and blood vessels. Important recent advances have been made in biomatrix design for IVD repair and in the oriented and dynamic culture of annular fibrochondrocytes into planar, spatially relevant, annular type structures. The development of hyaluronan hydrogels capable of rapid in situ gelation offer the possibility of supplementation of matrices with cells and other biomimetics and represent a significant advance in biopolymer design. New generation biological glues and self-curing acrylic formulations which may be augmented with slow delivery biomimetics in microcarriers may also find application in the non-surgical repair of annular defects. Despite major advances, significant technical challenges still have to be overcome before the biological repair of this intractable connective tissue becomes a realistic alternative to conventional surgical intervention for the treatment of chronic degenerate IVDs.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

References

  1. Abe T, Yamada H, Nakajima H, Kikuchi T, Takaishi H, Tadakuma T et al (2003) Repair of full-thickness cartilage defects using liposomal transforming growth factor-beta1. J Orthop Sci 8:92–101. doi:10.1007/s007760300016

    Article  PubMed  CAS  Google Scholar 

  2. Abreu JG, Ketpura NI, Reversade B, De Robertis EM (2002) Connective-tissue growth factor (CTGF) modulates cell signalling by BMP and TGF-beta. Nat Cell Biol 4:599–604

    PubMed  CAS  Google Scholar 

  3. Acosta FL Jr, Lotz J, Ames CP (2005) The potential role of mesenchymal stem cell therapy for intervertebral disc degeneration: a critical overview. Neurosurg Focus 19:E4. doi:10.3171/foc.2005.19.3.5

    Article  PubMed  Google Scholar 

  4. Agrawal A, Guttapalli A, Narayan S, Albert TJ, Shapiro IM, Risbud MV (2007) Normoxic stabilization of HIF-1alpha drives glycolytic metabolism and regulates aggrecan gene expression in nucleus pulposus cells of the rat intervertebral disk. Am J Physiol Cell Physiol 293:C621–C631. doi:10.1152/ajpcell.00538.2006

    Article  PubMed  CAS  Google Scholar 

  5. Alini M, Li W, Markovic P, Aebi M, Spiro RC, Roughley PJ (2003) The potential and limitations of a cell-seeded collagen/hyaluronan scaffold to engineer an intervertebral disc-like matrix. Spine 28:446–454. doi:10.1097/00007632-200303010-00007 discussion, p 453

    Article  PubMed  Google Scholar 

  6. Allen JM, Bateman JF, Hansen U, Wilson R, Bruckner P, Owens RT et al (2006) WARP is a novel multimeric component of the chondrocyte pericellular matrix that interacts with perlecan. J Biol Chem 281:7341–7349. doi:10.1074/jbc.M513746200

    Article  PubMed  CAS  Google Scholar 

  7. An HS, Takegami K, Kamada H, Nguyen CM, Thonar EJ, Singh K et al (2005) Intradiscal administration of osteogenic protein-1 increases intervertebral disc height and proteoglycan content in the nucleus pulposus in normal adolescent rabbits. Spine 30:25–31 discussion, pp 31–22

    PubMed  Google Scholar 

  8. Bengtsson E, Morgelin M, Sasaki T, Timpl R, Heinegard D, Aspberg A (2002) The leucine-rich repeat protein PRELP binds perlecan and collagens and may function as a basement membrane anchor. J Biol Chem 277:15061–15068. doi:10.1074/jbc.M108285200

    Article  PubMed  CAS  Google Scholar 

  9. Bobacz K, Ullrich R, Amoyo L, Erlacher L, Smolen JS, Graninger WB (2006) Stimulatory effects of distinct members of the bone morphogenetic protein family on ligament fibroblasts. Ann Rheum Dis 65:169–177. doi:10.1136/ard.2004.022756

    Article  PubMed  CAS  Google Scholar 

  10. Buckwalter JA, Cooper RR, Maynard JA (1976) Elastic fibers in human intervertebral discs. J Bone Joint Surg Am 58:73–76

    PubMed  CAS  Google Scholar 

  11. Burg MB, Ferraris JD, Dmitrieva NI (2007) Cellular response to hyperosmotic stresses. Physiol Rev 87:1441–1474. doi:10.1152/physrev.00056.2006

    Article  PubMed  CAS  Google Scholar 

  12. Cao L, Guilak F, Setton LA (2007) Three-dimensional morphology of the pericellular matrix of intervertebral disc cells in the rat. J Anat 211:444–452

    PubMed  Google Scholar 

  13. Casper CL, Yang W, Farach-Carson MC, Rabolt JF (2007) Coating electrospun collagen and gelatin fibers with perlecan domain I for increased growth factor binding. Biomacromolecules 8:1116–1123. doi:10.1021/bm061003s

    Article  PubMed  CAS  Google Scholar 

  14. Chakravarti S (2002) Functions of lumican and fibromodulin: lessons from knockout mice. Glycoconj J 19:287–293. doi:10.1023/A:1025348417078

    Article  PubMed  CAS  Google Scholar 

  15. Chang G, Kim HJ, Kaplan D, Vunjak-Novakovic G, Kandel RA (2007) Porous silk scaffolds can be used for tissue engineering annulus fibrosus. Eur Spine J 16:1848–1857. doi:10.1007/s00586-007-0364-4

    Article  PubMed  CAS  Google Scholar 

  16. Chen WH, Lo WC, Lee JJ, Su CH, Lin CT, Liu HY et al (2006) Tissue-engineered intervertebral disc and chondrogenesis using human nucleus pulposus regulated through TGF-beta1 in platelet-rich plasma. J Cell Physiol 209:744–754. doi:10.1002/jcp.20765

    Article  PubMed  CAS  Google Scholar 

  17. Cook SD, Patron LP, Salkeld SL, Rueger DC (2003) Repair of articular cartilage defects with osteogenic protein-1 (BMP-7) in dogs. J Bone Joint Surg Am 85-A(Suppl 3):116–123

    PubMed  Google Scholar 

  18. Corsi A, Xu T, Chen XD, Boyde A, Liang J, Mankani M et al (2002) Phenotypic effects of biglycan deficiency are linked to collagen fibril abnormalities, are synergized by decorin deficiency, and mimic Ehlers–Danlos-like changes in bone and other connective tissues. J Bone Miner Res 17:1180–1189. doi:10.1359/jbmr.2002.17.7.1180

    Article  PubMed  CAS  Google Scholar 

  19. Costell M, Gustafsson E, Aszodi A, Morgelin M, Bloch W, Hunziker E et al (1999) Perlecan maintains the integrity of cartilage and some basement membranes. J Cell Biol 147:1109–1122. doi:10.1083/jcb.147.5.1109

    Article  PubMed  CAS  Google Scholar 

  20. Di Cristofano C, Minervini A, Menicagli M, Salinitri G, Bertacca G, Pefanis G et al (2007) Nuclear expression of hypoxia-inducible factor-1alpha in clear cell renal cell carcinoma is involved in tumor progression. Am J Surg Pathol 31:1875–1881. doi:10.1097/PAS.0b013e318094fed8

    Article  PubMed  Google Scholar 

  21. Du Z, Fujiyama C, Chen Y, Masaki Z (2003) Expression of hypoxia-inducible factor 1alpha in human normal, benign, and malignant prostate tissue. Chin Med J (Engl) 116:1936–1939

    CAS  Google Scholar 

  22. Duncan NA (2006) Cell deformation and micromechanical environment in the intervertebral disc. J Bone Joint Surg Am 88(Suppl 2):47–51. doi:10.2106/JBJS.F.00035

    Article  PubMed  Google Scholar 

  23. Errington RJ, Puustjarvi K, White IR, Roberts S, Urban JP (1998) Characterisation of cytoplasm-filled processes in cells of the intervertebral disc. J Anat 192(Pt 3):369–378. doi:10.1046/j.1469-7580.1998.19230369.x

    Article  PubMed  Google Scholar 

  24. Eyre DR, Muir H (1976) Types I and II collagens in intervertebral disc. Interchanging radial distributions in annulus fibrosus. Biochem J 157:267–270

    PubMed  CAS  Google Scholar 

  25. Ezura Y, Chakravarti S, Oldberg A, Chervoneva I, Birk DE (2000) Differential expression of lumican and fibromodulin regulate collagen fibrillogenesis in developing mouse tendons. J Cell Biol 151:779–788. doi:10.1083/jcb.151.4.779

    Article  PubMed  CAS  Google Scholar 

  26. Fazzalari NL, Costi JJ, Hearn TC, Fraser RD, Vernon-Roberts B, Hutchinson J et al (2001) Mechanical and pathologic consequences of induced concentric anular tears in an ovine model. Spine 26:2575–2581. doi:10.1097/00007632-200112010-00010

    Article  PubMed  CAS  Google Scholar 

  27. Feng H, Danfelter M, Stromqvist B, Heinegard D (2006) Extracellular matrix in disc degeneration. J Bone Joint Surg Am 88(Suppl 2):25–29. doi:10.2106/JBJS.E.01341

    Article  PubMed  Google Scholar 

  28. Fujita N, Miyamoto T, Imai J, Hosogane N, Suzuki T, Yagi M et al (2005) CD24 is expressed specifically in the nucleus pulposus of intervertebral discs. Biochem Biophys Res Commun 338:1890–1896. doi:10.1016/j.bbrc.2005.10.166

    Article  PubMed  CAS  Google Scholar 

  29. Fujiwara S, Nakagawa K, Harada H, Nagato S, Furukawa K, Teraoka M et al (2007) Silencing hypoxia-inducible factor-1alpha inhibits cell migration and invasion under hypoxic environment in malignant gliomas. Int J Oncol 30:793–802

    PubMed  CAS  Google Scholar 

  30. Ganey T, Libera J, Moos V, Alasevic O, Fritsch KG, Meisel HJ et al (2003) Disc chondrocyte transplantation in a canine model: a treatment for degenerated or damaged intervertebral disc. Spine 28:2609–2620. doi:10.1097/01.BRS.0000097891.63063.78

    Article  PubMed  Google Scholar 

  31. Ghosh K, Ingber DE (2007) Micromechanical control of cell and tissue development: implications for tissue engineering. Adv Drug Deliv Rev 59:1306–1318. doi:10.1016/j.addr.2007.08.014

    Article  PubMed  CAS  Google Scholar 

  32. Gilson A, Dreger M, Urban J (2008) Towards the identification of intervertebral disc biomarkers: their role in tissue engineering for degenerated disc repair. In: Proceedings of World Forum for Spine Research, Kyoto, Japan, 23–26 January 2008

  33. Gorensek M, Jaksimovic C, Kregar-Velikonja N, Gorensek M, Knezevic M, Jeras M et al (2004) Nucleus pulposus repair with cultured autologous elastic cartilage derived chondrocytes. Cell Mol Biol Lett 9:363–373

    PubMed  Google Scholar 

  34. Graham LD, Glattauer V, Huson MG, Maxwell JM, Knott RB, White JW et al (2005) Characterization of a protein-based adhesive elastomer secreted by the Australian frog Notaden bennetti. Biomacromolecules 6:3300–3312. doi:10.1021/bm050335e

    Article  PubMed  CAS  Google Scholar 

  35. Graham LD, Glattauer V, Peng YY, Vaughan PR, Werkmeister JA, Tyler MT et al (2006) An adhesive secreted by Australian frogs of the genus Notaden. In: Smith AM, Callow JA (eds) Biological adhesives. Springer, Berlin, pp 207–233

    Chapter  Google Scholar 

  36. Grimaud E, Heymann D, Redini F (2002) Recent advances in TGF-beta effects on chondrocyte metabolism. Potential therapeutic roles of TGF-beta in cartilage disorders. Cytokine Growth Factor Rev 13:241–257. doi:10.1016/S1359-6101(02)00004-7

    Article  PubMed  CAS  Google Scholar 

  37. Gruber HE, Ingram JA, Hanley EN Jr (2007) Morphologic complexity of the pericellular matrix in the annulus of the human intervertebral disc. Biotech Histochem 82:217–225. doi:10.1080/10520290701713999

    Article  PubMed  CAS  Google Scholar 

  38. Guilak F, Alexopoulos LG, Upton ML, Youn I, Choi JB, Cao L et al (2006) The pericellular matrix as a transducer of biomechanical and biochemical signals in articular cartilage. Ann N Y Acad Sci 1068:498–512. doi:10.1196/annals.1346.011

    Article  PubMed  CAS  Google Scholar 

  39. Ha KY, Koh IJ, Kirpalani PA, Kim YY, Cho YK, Khang GS et al (2006) The expression of hypoxia inducible factor-1alpha and apoptosis in herniated discs. Spine 31:1309–1313. doi:10.1097/01.brs.0000219493.76081.d6

    Article  PubMed  Google Scholar 

  40. Helen W, Merry CL, Blaker JJ, Gough JE (2007) Three-dimensional culture of annulus fibrosus cells within PDLLA/Bioglass composite foam scaffolds: assessment of cell attachment, proliferation and extracellular matrix production. Biomaterials 28:2010–2020. doi:10.1016/j.biomaterials.2007.01.011

    Article  PubMed  CAS  Google Scholar 

  41. Helm GA, Gazit Z (2005) Future uses of mesenchymal stem cells in spine surgery. Neurosurg Focus 19:E13. doi:10.3171/foc.2005.19.6.14

    Article  PubMed  Google Scholar 

  42. Hidaka C, Goodrich LR, Chen CT, Warren RF, Crystal RG, Nixon AJ (2003) Acceleration of cartilage repair by genetically modified chondrocytes over expressing bone morphogenetic protein-7. J Orthop Res 21:573–583. doi:10.1016/S0736-0266(02)00264-4

    Article  PubMed  CAS  Google Scholar 

  43. Holland TA, Tessmar JK, Tabata Y, Mikos AG (2004) Transforming growth factor-beta 1 release from oligo(poly(ethylene glycol) fumarate) hydrogels in conditions that model the cartilage wound healing environment. J Control Rel 94:101–114. doi:10.1016/j.jconrel.2003.09.007

    Article  CAS  Google Scholar 

  44. Holm S, Maroudas A, Urban JP, Selstam G, Nachemson A (1981) Nutrition of the intervertebral disc: solute transport and metabolism. Connect Tissue Res 8:101–119

    Article  PubMed  CAS  Google Scholar 

  45. Hopf M, Gohring W, Kohfeldt E, Yamada Y, Timpl R (1999) Recombinant domain IV of perlecan binds to nidogens, laminin-nidogen complex, fibronectin, fibulin-2 and heparin. Eur J Biochem 259:917–925. doi:10.1046/j.1432-1327.1999.00127.x

    Article  PubMed  CAS  Google Scholar 

  46. Horikawa O, Nakajima H, Kikuchi T, Ichimura S, Yamada H, Fujikawa K et al (2004) Distribution of type VI collagen in chondrocyte microenvironment: study of chondrons isolated from human normal and degenerative articular cartilage and cultured chondrocytes. J Orthop Sci 9:29–36. doi:10.1007/s00776-003-0737-4

    Article  PubMed  CAS  Google Scholar 

  47. Horner HA, Urban JP (2001) 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. Spine 26:2543–2549. doi:10.1097/00007632-200112010-00006

    Article  PubMed  CAS  Google Scholar 

  48. Humzah MD, Soames RW (1988) Human intervertebral disc: structure and function. Anat Rec 220:337–356. doi:10.1002/ar.1092200402

    Article  PubMed  CAS  Google Scholar 

  49. Ingber DE (1997) Tensegrity: the architectural basis of cellular mechanotransduction. Annu Rev Physiol 59:575–599. doi:10.1146/annurev.physiol.59.1.575

    Article  PubMed  CAS  Google Scholar 

  50. Ingber DE (2003) Tensegrity I. Cell structure and hierarchical systems biology. J Cell Sci 116:1157–1173. doi:10.1242/jcs.00359

    Article  PubMed  CAS  Google Scholar 

  51. Ingber DE (2003) Tensegrity II. How structural networks influence cellular information processing networks. J Cell Sci 116:1397–1408. doi:10.1242/jcs.00360

    Article  PubMed  CAS  Google Scholar 

  52. Ingber DE (2006) Cellular mechanotransduction: putting all the pieces together again. FASEB J 20:811–827. doi:10.1096/fj.05-5424rev

    Article  PubMed  CAS  Google Scholar 

  53. Ingber DE, Mow VC, Butler D, Niklason L, Huard J, Mao J et al (2006) Tissue engineering and developmental biology: going biomimetic. Tissue Eng 12:3265–3283. doi:10.1089/ten.2006.12.3265

    Article  PubMed  CAS  Google Scholar 

  54. Iozzo RV (2005) Basement membrane proteoglycans: from cellar to ceiling. Nat Rev Mol Cell Biol 6:646–656. doi:10.1038/nrm1702

    Article  PubMed  CAS  Google Scholar 

  55. Isogai N, Kusuhara H, Ikada Y, Ohtani H, Jacquet R, Hillyer J et al (2006) Comparison of different chondrocytes for use in tissue engineering of cartilage model structures. Tissue Eng 12:691–703. doi:10.1089/ten.2006.12.691

    Article  PubMed  CAS  Google Scholar 

  56. Isogai Z, Aspberg A, Keene DR, Ono RN, Reinhardt DP, Sakai LY (2002) Versican interacts with fibrillin-1 and links extracellular microfibrils to other connective tissue networks. J Biol Chem 277:4565–4572. doi:10.1074/jbc.M110583200

    Article  PubMed  CAS  Google Scholar 

  57. Jelic M, Pecina M, Haspl M, Kos J, Taylor K, Maticic D et al (2001) Regeneration of articular cartilage chondral defects by osteogenic protein-1 (bone morphogenetic protein-7) in sheep. Growth Factors 19:101–113

    Article  PubMed  CAS  Google Scholar 

  58. Ji Y, Ghosh K, Shu XZ, Li B, Sokolov JC, Prestwich GD et al (2006) Electrospun three-dimensional hyaluronic acid nanofibrous scaffolds. Biomaterials 27:3782–3792. doi:10.1016/j.biomaterials.2006.02.037

    Article  PubMed  CAS  Google Scholar 

  59. Johnson WE, Eisenstein SM, Roberts S (2001) Cell cluster formation in degenerate lumbar intervertebral discs is associated with increased disc cell proliferation. Connect Tissue Res 42:197–207. doi:10.3109/03008200109005650

    Article  PubMed  CAS  Google Scholar 

  60. Johnson WE, Roberts S (2003) Human intervertebral disc cell morphology and cytoskeletal composition: a preliminary study of regional variations in health and disease. J Anat 203:605–612. doi:10.1046/j.1469-7580.2003.00249.x

    Article  PubMed  CAS  Google Scholar 

  61. Johnson WE, Wootton A, El Haj A, Eisenstein SM, Curtis AS, Roberts S (2006) Topographical guidance of intervertebral disc cell growth in vitro: towards the development of tissue repair strategies for the anulus fibrosus. Eur Spine J 15(Suppl 3):S389–S396. doi:10.1007/s00586-006-0125-9

    Article  PubMed  Google Scholar 

  62. Kallunki P, Tryggvason K (1992) Human basement membrane heparan sulfate proteoglycan core protein: a 467-kD protein containing multiple domains resembling elements of the low density lipoprotein receptor, laminin, neural cell adhesion molecules, and epidermal growth factor. J Cell Biol 116:559–571. doi:10.1083/jcb.116.2.559

    Article  PubMed  CAS  Google Scholar 

  63. Knox S, Melrose J, Whitelock J (2001) Electrophoretic, biosensor, and bioactivity analyses of perlecans of different cellular origins. Proteomics 1:1534–1541 10.1002/1615-9861(200111)1:12≤1534::AID-PROT1534≥3.0.CO;2-A

    Article  PubMed  CAS  Google Scholar 

  64. Knox S, Merry C, Stringer S, Melrose J, Whitelock J (2002) Not all perlecans are created equal: interactions with fibroblast growth factor (FGF) 2 and FGF receptors. J Biol Chem 277:14657–14665

    PubMed  CAS  Google Scholar 

  65. Knox SM, Whitelock JM (2006) Perlecan: how does one molecule do so many things? Cell Mol Life Sci 63:2435–2445. doi:10.1007/s00018-006-6162-z

    Article  PubMed  CAS  Google Scholar 

  66. Larraz E, Elvira C, Fernandez M, Parra J, Collia F, Lopez-Bravo A et al (2007) Self-curing acrylic formulations with applications in intervertebral disk restoration: drug release and biological behaviour. J Tissue Eng Regen Med 1:120–127. doi:10.1002/term.10

    Article  PubMed  CAS  Google Scholar 

  67. Lee CR, Sakai D, Nakai T, Toyama K, Mochida J, Alini M et al (2007) A phenotypic comparison of intervertebral disc and articular cartilage cells in the rat. Eur Spine J 16:2174–2185. doi:10.1007/s00586-007-0475-y

    Article  PubMed  Google Scholar 

  68. Li F, Li B, Wang QM, Wang JH (2008) Cell shape regulates collagen type I expression in human tendon fibroblasts. Cell Motil Cytoskeleton 65(4):332–341

    Article  PubMed  CAS  Google Scholar 

  69. Lilley KS, Friedman DB (2004) All about DIGE: quantification technology for differential-display 2D-gel proteomics. Expert Rev Proteomics 1:401–409. doi:10.1586/14789450.1.4.401

    Article  PubMed  CAS  Google Scholar 

  70. Maniotis AJ, Chen CS, Ingber DE (1997) Demonstration of mechanical connections between integrins, cytoskeletal filaments, and nucleoplasm that stabilize nuclear structure. Proc Natl Acad Sci USA 94:849–854. doi:10.1073/pnas.94.3.849

    Article  PubMed  CAS  Google Scholar 

  71. Mano JF, Reis RL (2007) Osteochondral defects: present situation and tissue engineering approaches. J Tissue Eng Regen Med 1:261–273. doi:10.1002/term.37

    Article  PubMed  CAS  Google Scholar 

  72. Maroudas A, Stockwell RA, Nachemson A, Urban J (1975) Factors involved in the nutrition of the human lumbar intervertebral disc: cellularity and diffusion of glucose in vitro. J Anat 120:113–130

    PubMed  CAS  Google Scholar 

  73. Meisel HJ, Siodla V, Ganey T, Minkus Y, Hutton WC, Alasevic OJ (2007) Clinical experience in cell-based therapeutics: disc chondrocyte transplantation A treatment for degenerated or damaged intervertebral disc. Biomol Eng 24:5–21. doi:10.1016/j.bioeng.2006.07.002

    Article  PubMed  CAS  Google Scholar 

  74. Melrose J, Ghosh P, Taylor TK (2001) A comparative analysis of the differential spatial and temporal distributions of the large (aggrecan, versican) and small (decorin, biglycan, fibromodulin) proteoglycans of the intervertebral disc. J Anat 198:3–15. doi:10.1046/j.1469-7580.2001.19810003.x

    Article  PubMed  CAS  Google Scholar 

  75. Melrose J, Ghosh P, Taylor TK, Hall A, Osti OL, Vernon-Roberts B et al (1992) A longitudinal study of the matrix changes induced in the intervertebral disc by surgical damage to the annulus fibrosus. J Orthop Res 10:665–676. doi:10.1002/jor.1100100509

    Article  PubMed  CAS  Google Scholar 

  76. Melrose J, Ghosh P, Taylor TK, Latham J, Moore R (1997) Topographical variation in the catabolism of aggrecan in an ovine annular lesion model of experimental disc degeneration. J Spinal Disord 10:55–67. doi:10.1097/00002517-199702000-00008

    Article  PubMed  CAS  Google Scholar 

  77. Melrose J, Ghosh P, Taylor TK, Vernon-Roberts B, Latham J, Moore R (1997) Elevated synthesis of biglycan and decorin in an ovine annular lesion model of experimental disc degeneration. Eur Spine J 6:376–384. doi:10.1007/BF01834063

    Article  PubMed  CAS  Google Scholar 

  78. Melrose J, Hayes AJ, Whitelock JM, Little CB (2008) Perlecan, the “jack of all trades” proteoglycan of cartilaginous weight-bearing connective tissues. Bioessays 30:457–469. doi:10.1002/bies.20748

    Article  PubMed  CAS  Google Scholar 

  79. Melrose J, Roberts S, Smith S, Menage J, Ghosh P (2002) Increased nerve and blood vessel ingrowth associated with proteoglycan depletion in an ovine anular lesion model of experimental disc degeneration. Spine 27:1278–1285. doi:10.1097/00007632-200206150-00007

    Article  PubMed  Google Scholar 

  80. Melrose J, Smith S, Ghosh P (2000) Differential expression of proteoglycan epitopes by ovine intervertebral disc cells. J Anat 197(Pt 2):189–198. doi:10.1046/j.1469-7580.2000.19720189.x

    Article  PubMed  CAS  Google Scholar 

  81. Melrose J, Smith S, Little CB, Kitson J, Hwa SY, Ghosh P (2002) Spatial and temporal localization of transforming growth factor-beta, fibroblast growth factor-2, and osteonectin, and identification of cells expressing alpha-smooth muscle actin in the injured anulus fibrosus: implications for extracellular matrix repair. Spine 27:1756–1764. doi:10.1097/00007632-200208150-00014

    Article  PubMed  Google Scholar 

  82. Melrose J, Smith SM, Appleyard RC, Little CB (2007) Aggrecan, versican and type VI collagen are components of annular translamellar crossbridges in the intervertebral disc. Eur Spine J 17(2):314–324

    Article  PubMed  Google Scholar 

  83. Melrose J, Smith SM, Fuller ES, Young AA, Roughley PJ, Dart A et al (2007) Biglycan and fibromodulin fragmentation correlates with temporal and spatial annular remodelling in experimentally injured ovine intervertebral discs. Eur Spine J 16:2193–2205. doi:10.1007/s00586-007-0497-5

    Article  PubMed  Google Scholar 

  84. Mierisch CM, Cohen SB, Jordan LC, Robertson PG, Balian G, Diduch DR (2002) Transforming growth factor-beta in calcium alginate beads for the treatment of articular cartilage defects in the rabbit. Arthroscopy 18:892–900. doi:10.1053/jars.2002.36117

    Article  PubMed  Google Scholar 

  85. Mikos AG, Herring SW, Ochareon P, Elisseeff J, Lu HH, Kandel R et al (2006) Engineering complex tissues. Tissue Eng 12:3307–3339. doi:10.1089/ten.2006.12.3307

    Article  PubMed  CAS  Google Scholar 

  86. Minamide A, Hashizume H, Yoshida M, Kawakami M, Hayashi N, Tamaki T (1999) Effects of basic fibroblast growth factor on spontaneous resorption of herniated intervertebral discs. An experimental study in the rabbit. Spine 24:940–945. doi:10.1097/00007632-199905150-00003

    Article  PubMed  CAS  Google Scholar 

  87. Miosge N, Simniok T, Sprysch P, Herken R (2003) The collagen type XVIII endostatin domain is co-localized with perlecan in basement membranes in vivo. J Histochem Cytochem 51:285–296

    PubMed  CAS  Google Scholar 

  88. Mizuno H, Roy AK, Vacanti CA, Kojima K, Ueda M, Bonassar LJ (2004) Tissue-engineered composites of anulus fibrosus and nucleus pulposus for intervertebral disc replacement. Spine 29:1290–1297. doi:10.1097/01.BRS.0000128264.46510.27 discussion, pp 1297–1298

    Article  PubMed  Google Scholar 

  89. Mizuno H, Roy AK, Zaporojan V, Vacanti CA, Ueda M, Bonassar LJ (2006) Biomechanical and biochemical characterization of composite tissue-engineered intervertebral discs. Biomaterials 27:362–370. doi:10.1016/j.biomaterials.2005.06.042

    Article  PubMed  CAS  Google Scholar 

  90. Moore RJ, Crotti TN, Osti OL, Fraser RD, Vernon-Roberts B (1999) Osteoarthrosis of the facet joints resulting from anular rim lesions in sheep lumbar discs. Spine 24:519–525. doi:10.1097/00007632-199903150-00003

    Article  PubMed  CAS  Google Scholar 

  91. Moore RJ, Latham JM, Vernon-Roberts B, Fraser RD (1994) Does plate fixation prevent disc degeneration after a lateral anulus tear? Spine 19:2787–2790. doi:10.1097/00007632-199412150-00010

    Article  PubMed  CAS  Google Scholar 

  92. Moore RJ, Osti OL, Vernon-Roberts B, Fraser RD (1992) Changes in endplate vascularity after an outer anulus tear in the sheep. Spine 17:874–878. doi:10.1097/00007632-199208000-00003

    Article  PubMed  CAS  Google Scholar 

  93. Moore RJ, Vernon-Roberts B, Osti OL, Fraser RD (1996) Remodeling of vertebral bone after outer anular injury in sheep. Spine 21:936–940. doi:10.1097/00007632-199604150-00006

    Article  PubMed  CAS  Google Scholar 

  94. Murdoch AD, Dodge GR, Cohen I, Tuan RS, Iozzo RV (1992) Primary structure of the human heparan sulfate proteoglycan from basement membrane (HSPG2/perlecan). A chimeric molecule with multiple domains homologous to the low density lipoprotein receptor, laminin, neural cell adhesion molecules, and epidermal growth factor. J Biol Chem 267:8544–8557

    PubMed  CAS  Google Scholar 

  95. Mwale F, Iordanova M, Demers CN, Steffen T, Roughley P, Antoniou J (2005) Biological evaluation of chitosan salts cross-linked to genipin as a cell scaffold for disk tissue engineering. Tissue Eng 11:130–140. doi:10.1089/ten.2005.11.130

    Article  PubMed  CAS  Google Scholar 

  96. Mwale F, Roughley P, Antoniou J (2004) Distinction between the extracellular matrix of the nucleus pulposus and hyaline cartilage: a requisite for tissue engineering of intervertebral disc. Eur Cell Mater 8:58–63 discussion, pp 63–54

    PubMed  CAS  Google Scholar 

  97. Nagano T, Yonenobu K, Miyamoto S, Tohyama M, Ono K (1995) Distribution of the basic fibroblast growth factor and its receptor gene expression in normal and degenerated rat intervertebral discs. Spine 20:1972–1978. doi:10.1097/00007632-199509150-00002

    Article  PubMed  CAS  Google Scholar 

  98. Neidlinger-Wilke C, Wurtz K, Urban JP, Borm W, Arand M, Ignatius A et al (2006) Regulation of gene expression in intervertebral disc cells by low and high hydrostatic pressure. Eur Spine J 15(Suppl 3):S372–S378. doi:10.1007/s00586-006-0112-1

    Article  PubMed  Google Scholar 

  99. Nerurkar NL, Elliott DM, Mauck RL (2007) Mechanics of oriented electrospun nanofibrous scaffolds for annulus fibrosus tissue engineering. J Orthop Res 25(8):1018–1028

    Article  PubMed  CAS  Google Scholar 

  100. Ninan L, Stroshine RL, Wilker JJ, Shi R (2007) Adhesive strength and curing rate of marine mussel protein extracts on porcine small intestinal submucosa. Acta Biomater 3(5):687–694

    Article  PubMed  CAS  Google Scholar 

  101. Nishida T, Kubota S, Fukunaga T, Kondo S, Yosimichi G, Nakanishi T et al (2003) CTGF/Hcs24, hypertrophic chondrocyte-specific gene product, interacts with perlecan in regulating the proliferation and differentiation of chondrocytes. J Cell Physiol 196:265–275. doi:10.1002/jcp. 10277

    Article  PubMed  CAS  Google Scholar 

  102. Noonan DM, Fulle A, Valente P, Cai S, Horigan E, Sasaki M et al (1991) The complete sequence of perlecan, a basement membrane heparan sulfate proteoglycan, reveals extensive similarity with laminin A chain, low density lipoprotein-receptor, and the neural cell adhesion molecule. J Biol Chem 266:22939–22947

    PubMed  CAS  Google Scholar 

  103. Osti OL, Vernon-Roberts B, Fraser RD (1990) 1990 Volvo Award in experimental studies. Anulus tears and intervertebral disc degeneration. An experimental study using an animal model. Spine 15:762–767. doi:10.1097/00007632-199008010-00005

    Article  PubMed  CAS  Google Scholar 

  104. Osti OL, Vernon-Roberts B, Moore R, Fraser RD (1992) Annular tears and disc degeneration in the lumbar spine. A post-mortem study of 135 discs. J Bone Joint Surg Br 74:678–682

    PubMed  CAS  Google Scholar 

  105. Pattison ST, Melrose J, Ghosh P, Taylor TK (2001) Regulation of gelatinase-A (MMP-2) production by ovine intervertebral disc nucleus pulposus cells grown in alginate bead culture by Transforming Growth Factor-beta(1) and insulin like growth factor-I. Cell Biol Int 25:679–689. doi:10.1006/cbir.2000.0718

    Article  PubMed  CAS  Google Scholar 

  106. Pezowicz CA, Robertson PA, Broom ND (2005) Intralamellar relationships within the collagenous architecture of the annulus fibrosus imaged in its fully hydrated state. J Anat 207:299–312. doi:10.1111/j.1469-7580.2005.00467.x

    Article  PubMed  Google Scholar 

  107. Poole CA, Ayad S, Gilbert RT (1992) Chondrons from articular cartilage. V. Immunohistochemical evaluation of type VI collagen organisation in isolated chondrons by light, confocal and electron microscopy. J Cell Sci 103(Pt 4):1101–1110

    PubMed  CAS  Google Scholar 

  108. Rajasekaran S (2008) Evaluation of disc nutrition by serial post contrast MRI studies. In: Proceedings world forum for spine research, Kyoto, Japan, p 49

  109. Rajpurohit R, Risbud MV, Ducheyne P, Vresilovic EJ, Shapiro IM (2002) Phenotypic characteristics of the nucleus pulposus: expression of hypoxia inducing factor-1, glucose transporter-1 and MMP-2. Cell Tissue Res 308:401–407. doi:10.1007/s00441-002-0563-6

    Article  PubMed  CAS  Google Scholar 

  110. Ramirez F, Rifkin DB (2003) Cell signalling events: a view from the matrix. Matrix Biol 22:101–107. doi:10.1016/S0945-053X(03)00002-7

    Article  PubMed  CAS  Google Scholar 

  111. Revell PA, Damien E, Di Silvio L, Gurav N, Longinotti C, Ambrosio L (2007) Tissue engineered intervertebral disc repair in the pig using injectable polymers. J Mater Sci Mater Med 18:303–308. doi:10.1007/s10856-006-0693-6

    Article  PubMed  CAS  Google Scholar 

  112. Richardson SM (2007) Tissue engineering today, not tomorrow. Regen Med 2:91–94. doi:10.2217/17460751.2.1.91

    Article  PubMed  Google Scholar 

  113. Richardson SM, Curran JM, Chen R, Vaughan-Thomas A, Hunt JA, Freemont AJ et al (2006) The differentiation of bone marrow mesenchymal stem cells into chondrocyte-like cells on poly-L-lactic acid (PLLA) scaffolds. Biomaterials 27:4069–4078. doi:10.1016/j.biomaterials.2006.03.017

    Article  PubMed  CAS  Google Scholar 

  114. Richardson SM, Hughes N, Hunt JA, Freemont AJ, Hoyland JA (2008) Human mesenchymal stem cell differentiation to NP-like cells in chitosan-glycerophosphate hydrogels. Biomaterials 29:85–93. doi:10.1016/j.biomaterials.2007.09.018

    Article  PubMed  CAS  Google Scholar 

  115. Richardson SM, Knowles R, Tyler J, Mobasheri A, Hoyland JA (2008) Expression of glucose transporters GLUT-1, GLUT-3, GLUT-9 and HIF-1alpha in normal and degenerate human intervertebral disc. Histochem Cell Biol 129(4):503–511

    Article  PubMed  CAS  Google Scholar 

  116. Richardson SM, Mobasheri A, Freemont AJ, Hoyland JA (2007) Intervertebral disc biology, degeneration and novel tissue engineering and regenerative medicine therapies. Histol Histopathol 22:1033–1041

    PubMed  CAS  Google Scholar 

  117. Richardson SM, Walker RV, Parker S, Rhodes NP, Hunt JA, Freemont AJ et al (2006) Intervertebral disc cell-mediated mesenchymal stem cell differentiation. Stem Cells 24:707–716. doi:10.1634/stemcells.2005-0205

    Article  PubMed  CAS  Google Scholar 

  118. Risbud MV, Di Martino A, Guttapalli A, Seghatoleslami R, Denaro V, Vaccaro AR et al (2006) Toward an optimum system for intervertebral disc organ culture: TGF-beta 3 enhances nucleus pulposus and anulus fibrosus survival and function through modulation of TGF-beta-R expression and ERK signaling. Spine 31:884–890. doi:10.1097/01.brs.0000209335.57767.b5

    Article  PubMed  Google Scholar 

  119. Risbud MV, Guttapalli A, Stokes DG, Hawkins D, Danielson KG, Schaer TP et al (2006) Nucleus pulposus cells express HIF-1alpha under normoxic culture conditions: a metabolic adaptation to the intervertebral disc microenvironment. J Cell Biochem 98:152–159. doi:10.1002/jcb.20765

    Article  PubMed  CAS  Google Scholar 

  120. Roberts S, Ayad S, Menage PJ (1991) Immunolocalisation of type VI collagen in the intervertebral disc. Ann Rheum Dis 50:787–791

    Article  PubMed  CAS  Google Scholar 

  121. Robinson PS, Huang TF, Kazam E, Iozzo RV, Birk DE, Soslowsky LJ (2005) Influence of decorin and biglycan on mechanical properties of multiple tendons in knockout mice. J Biomech Eng 127:181–185. doi:10.1115/1.1835363

    Article  PubMed  Google Scholar 

  122. Roughley PJ (2006) The structure and function of cartilage proteoglycans. Eur Cell Mater 12:92–101

    PubMed  CAS  Google Scholar 

  123. Sakai D, Mochida J, Iwashina T, Hiyama A, Omi H, Imai M et al (2006) Regenerative effects of transplanting mesenchymal stem cells embedded in atelocollagen to the degenerated intervertebral disc. Biomaterials 27:335–345. doi:10.1016/j.biomaterials.2005.06.038

    Article  PubMed  CAS  Google Scholar 

  124. Sato M, Asazuma T, Ishihara M, Kikuchi T, Masuoka K, Ichimura S et al (2003) An atelocollagen honeycomb-shaped scaffold with a membrane seal (ACHMS-scaffold) for the culture of annulus fibrosus cells from an intervertebral disc. J Biomed Mater Res A 64:248–256. doi:10.1002/jbm.a.10287

    Article  PubMed  CAS  Google Scholar 

  125. Schmorl G, Junghans H (1971) The human spine in health and disease. 2nd American edition translated and edited by EF Besemann. Grune and Stratton, New York and London

  126. Schumann D, Ekaputra AK, Lam CX, Hutmacher DW (2007) Biomaterials/scaffolds. Design of bioactive, multiphasic PCL/collagen type I and type II-PCL-TCP/collagen composite scaffolds for functional tissue engineering of osteochondral repair tissue by using electrospinning and FDM techniques. Methods Mol Med 140:101–124

    Article  PubMed  CAS  Google Scholar 

  127. Sebastine IM, Williams DJ (2007) Current developments in tissue engineering of nucleus pulposus for the treatment of intervertebral disc degeneration. Conf Proc IEEE Eng Med Biol Soc 1:6400–6405. doi:10.1109/IEMBS.2007.4353821

    Google Scholar 

  128. Seguin CA, Grynpas MD, Pilliar RM, Waldman SD, Kandel RA (2004) Tissue engineered nucleus pulposus tissue formed on a porous calcium polyphosphate substrate. Spine 29:1299–1306. doi:10.1097/01.BRS.0000127183.43765.AF discussion, pp 1306–1297

    Article  PubMed  Google Scholar 

  129. Shao X, Hunter CJ (2007) Developing an alginate/chitosan hybrid fiber scaffold for annulus fibrosus cells. J Biomed Mater Res A 82(3):701–710

    PubMed  Google Scholar 

  130. Silverman RP, Bonasser L, Passaretti D, Randolph MA, Yaremchuk MJ (2000) Adhesion of tissue-engineered cartilage to native cartilage. Plast Reconstr Surg 105:1393–1398. doi:10.1097/00006534-200004040-00019

    Article  PubMed  CAS  Google Scholar 

  131. Smith LJ, Fazzalari NL (2006) Regional variations in the density and arrangement of elastic fibres in the anulus fibrosus of the human lumbar disc. J Anat 209:359–367. doi:10.1111/j.1469-7580.2006.00610.x

    Article  PubMed  Google Scholar 

  132. Steck E, Bertram H, Abel R, Chen B, Winter A, Richter W (2005) Induction of intervertebral disc-like cells from adult mesenchymal stem cells. Stem Cells 23:403–411. doi:10.1634/stemcells.2004-0107

    Article  PubMed  CAS  Google Scholar 

  133. Stevens MM, Marini RP, Martin I, Langer R, Prasad Shastri V (2004) FGF-2 enhances TGF-beta1-induced periosteal chondrogenesis. J Orthop Res 22:1114–1119. doi:10.1016/j.orthres.2003.12.021

    Article  PubMed  CAS  Google Scholar 

  134. Takegami K, Thonar EJ, An HS, Kamada H, Masuda K (2002) Osteogenic protein-1 enhances matrix replenishment by intervertebral disc cells previously exposed to interleukin-1. Spine 27:1318–1325. doi:10.1097/00007632-200206150-00014

    Article  PubMed  Google Scholar 

  135. Tannu NS, Hemby SE (2006) Two-dimensional fluorescence difference gel electrophoresis for comparative proteomics profiling. Nat Protocols 1:1732–1742. doi:10.1038/nprot.2006.256

    Article  CAS  Google Scholar 

  136. Thompson JP, Oegema TR Jr, Bradford DS (1991) Stimulation of mature canine intervertebral disc by growth factors. Spine 16:253–260. doi:10.1097/00007632-199103000-00001

    Article  PubMed  CAS  Google Scholar 

  137. Thompson RE, Pearcy MJ, Downing KJ, Manthey BA, Parkinson IH, Fazzalari NL (2000) Disc lesions and the mechanics of the intervertebral joint complex. Spine 25:3026–3035. doi:10.1097/00007632-200012010-00010

    Article  PubMed  CAS  Google Scholar 

  138. Tsai AD, Yeh LC, Lee JC (2003) Effects of osteogenic protein-1 (OP-1, BMP-7) on gene expression in cultured medial collateral ligament cells. J Cell Biochem 90:777–791. doi:10.1002/jcb.10666

    Article  PubMed  CAS  Google Scholar 

  139. Tsai TT, Danielson KG, Guttapalli A, Oguz E, Albert TJ, Shapiro IM et al (2006) TonEBP/OREBP is a regulator of nucleus pulposus cell function and survival in the intervertebral disc. J Biol Chem 281:25416–25424. doi:10.1074/jbc.M601969200

    Article  PubMed  CAS  Google Scholar 

  140. Tsai TT, Guttapalli A, Oguz E, Chen LH, Vaccaro AR, Albert TJ et al (2007) Fibroblast growth factor-2 maintains the differentiation potential of nucleus pulposus cells in vitro: implications for cell-based transplantation therapy. Spine 32:495–502. doi:10.1097/01.brs.0000257341.88880.f1

    Article  PubMed  Google Scholar 

  141. Tu H, Sasaki T, Snellman A, Gohring W, Pirila P, Timpl R et al (2002) The type XIII collagen ectodomain is a 150-nm rod and capable of binding to fibronectin, nidogen-2, perlecan, and heparin. J Biol Chem 277:23092–23099. doi:10.1074/jbc.M107583200

    Article  PubMed  CAS  Google Scholar 

  142. Turgut M, Uysal A, Uslu S, Tavus N, Yurtseven ME (2003) The effects of calcium channel antagonist nimodipine on end-plate vascularity of the degenerated intervertebral disc in rats. J Clin Neurosci 10:219–223. doi:10.1016/S0967-5868(02)00336-3

    Article  PubMed  CAS  Google Scholar 

  143. Urban JP, Holm S, Maroudas A, Nachemson A (1977) Nutrition of the intervertebral disk. An in vivo study of solute transport. Clin Orthop Relat Res 129:101–114

    PubMed  CAS  Google Scholar 

  144. Urban JP, Smith S, Fairbank JC (2004) Nutrition of the intervertebral disc. Spine 29:2700–2709. doi:10.1097/01.brs.0000146499.97948.52

    Article  PubMed  Google Scholar 

  145. Vernengo J, Fussell GW, Smith NG, Lowman AM (2007) Evaluation of novel injectable hydrogels for nucleus pulposus replacement. J Biomed Mater Res B Appl Biomater 84(1):64–69

    Google Scholar 

  146. Vernon-Roberts B, Moore RJ, Fraser RD (2007) The natural history of age related disc degeneration. The pathology and sequelae of tears. Spine 32(25):2797-2804

    Google Scholar 

  147. Vincent T, Hermansson M, Bolton M, Wait R, Saklatvala J (2002) Basic FGF mediates an immediate response of articular cartilage to mechanical injury. Proc Natl Acad Sci USA 99:8259–8264. doi:10.1073/pnas.122033199

    Article  PubMed  CAS  Google Scholar 

  148. Vincent T, Saklatvala J (2006) Basic fibroblast growth factor: an extracellular mechanotransducer in articular cartilage? Biochem Soc Trans 34:456–457. doi:10.1042/BST0340456

    Article  PubMed  CAS  Google Scholar 

  149. Vincent TL, Hermansson MA, Hansen UN, Amis AA, Saklatvala J (2004) Basic fibroblast growth factor mediates transduction of mechanical signals when articular cartilage is loaded. Arthritis Rheum 50:526–533. doi:10.1002/art.20047

    Article  PubMed  CAS  Google Scholar 

  150. Vincent TL, McLean CJ, Full LE, Peston D, Saklatvala J (2007) FGF-2 is bound to perlecan in the pericellular matrix of articular cartilage, where it acts as a chondrocyte mechanotransducer. Osteoarthr Cartil 15:752–763. doi:10.1016/j.joca.2007.01.021

    Article  PubMed  CAS  Google Scholar 

  151. Wan Y, Feng G, Shen FH, Balian G, Laurencin CT, Li X (2007) Novel biodegradable poly(1, 8-octanediol malate) for annulus fibrosus regeneration. Macromol Biosci 7:1217–1224. doi:10.1002/mabi.200700053

    Article  PubMed  CAS  Google Scholar 

  152. Wan Y, Feng G, Shen FH, Laurencin CT, Li X (2008) Biphasic scaffold for annulus fibrosus tissue regeneration. Biomaterials 29:643–652. doi:10.1016/j.biomaterials.2007.10.031

    Article  PubMed  CAS  Google Scholar 

  153. Whitelock JM, Ma JL, Davies N, Nielsen N, Chuang C, Rees M, Iozzo RV, Knox S, Lord M (2008) Recombinant heparan sulphate for use in tissue engineering applications. J Chem Technol Biotechnol 83:496–504. doi:10.1002/jctb.1835

    Article  CAS  Google Scholar 

  154. Wiberg C, Heinegard D, Wenglen C, Timpl R, Morgelin M (2002) Biglycan organizes collagen VI into hexagonal-like networks resembling tissue structures. J Biol Chem 277:49120–49126. doi:10.1074/jbc.M206891200

    Article  PubMed  CAS  Google Scholar 

  155. Wiberg C, Klatt AR, Wagener R, Paulsson M, Bateman JF, Heinegard D et al (2003) Complexes of matrilin-1 and biglycan or decorin connect collagen VI microfibrils to both collagen II and aggrecan. J Biol Chem 278:37698–37704. doi:10.1074/jbc.M304638200

    Article  PubMed  CAS  Google Scholar 

  156. Wilda H, Gough JE (2006) In vitro studies of annulus fibrosus disc cell attachment, differentiation and matrix production on PDLLA/45S5 Bioglass composite films. Biomaterials 27:5220–5229. doi:10.1016/j.biomaterials.2006.06.008

    Article  PubMed  CAS  Google Scholar 

  157. Wuertz K, Urban JP, Klasen J, Ignatius A, Wilke HJ, Claes L et al (2007) Influence of extracellular osmolarity and mechanical stimulation on gene expression of intervertebral disc cells. J Orthop Res 25:1513–1522. doi:10.1002/jor.20436

    Article  PubMed  CAS  Google Scholar 

  158. Yu J (2002) Elastic tissues of the intervertebral disc. Biochem Soc Trans 30:848–852. doi:10.1042/BST0300848

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

This study was funded by NHMRC Project Grant 211266.

Author information

Authors and Affiliations

  1. Raymond Purves Research Laboratory, Institute of Bone & Joint Research, Kolling Institute of Medical Research, University of Sydney, Royal North Shore Hospital, St. Leonards, NSW, 2065, Australia

    James Melrose, Susan M. Smith & Christopher B. Little

  2. The Adelaide Centre for Spinal Research, Institute of Medical and Veterinary Science, Hanson Institute, Frome Rd, Adelaide, SA, 5000, Australia

    Robert J. Moore, Barrie Vernon-Roberts & Robert D. Fraser

Authors
  1. James Melrose
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Susan M. Smith
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Christopher B. Little
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Robert J. Moore
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Barrie Vernon-Roberts
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Robert D. Fraser
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to James Melrose.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Melrose, J., Smith, S.M., Little, C.B. et al. Recent advances in annular pathobiology provide insights into rim-lesion mediated intervertebral disc degeneration and potential new approaches to annular repair strategies. Eur Spine J 17, 1131–1148 (2008). https://doi.org/10.1007/s00586-008-0712-z

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00586-008-0712-z

Keywords

Search

Navigation