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Biochemical composition and turnover of the extracellular matrix of the normal and degenerate intervertebral disc

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Abstract

Background

The intervertebral disc (IVD) is a complex cartilaginous structure which functions to resist biomechanical loads during spinal movement. It consists of the highly viscous cartilaginous nucleus pulposus, which is surrounded laterally by a thick outer ring of fibrous cartilage—the annulus fibrosus—and sandwiched inferiorly and superiorly by the cartilage end-plates. The main extracellular matrix molecules of the disc are collagens, proteoglycans, glycoproteins and elastin. The disc also contains appreciable amounts of water, matrix-degrading protease enzymes and their inhibitors, soluble signalling molecules and various metabolic breakdown products.

Methods

This review provides a comprehensive description of the biochemical composition of the extracellular matrix of the IVD and, specifically, the proteases involved in its molecular turnover. Quantitation of the turnover rates using racemization of aspartic acid as a molecular clock is also discussed.

Conclusions

Molecular turnover rates of the major constituent matrix macromolecules of the IVD are found to be particularly slow, especially in the case of collagen. Over a normal human life span, this slow turnover may compromise the structural integrity of the IVD extracellular matrix essential for normal physiological functioning.

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References

  1. Sivakamasundari V, Lufkin T (2012) Bridging the gap: understanding embryonic intervertebral disc development. Cell Dev Biol 1:1000103

    Google Scholar 

  2. Donohue PJ, Jahnke MR, Blaha JD et al (1988) Characterization of link protein(s) from human intervertebral-disc tissues. Biochem J 251:739–747

    CAS  PubMed Central  PubMed  Google Scholar 

  3. Eyre DR, Matsui Y, Wu JJ (2002) Collagen polymorphisms of the intervertebral disc. Biochem Soc Trans 30:844–848

    CAS  PubMed  Google Scholar 

  4. Franklin L, Hull EW (1966) Lipid content of the intervertebral disc. Clin Chem 12:253–257

    CAS  PubMed  Google Scholar 

  5. Oktay G, Guner A, Guner G et al (1995) Lipid analysis in human intervertebral disc material. Biochem Soc Trans 23:299S

    CAS  PubMed  Google Scholar 

  6. Ricard-Blum S, Ruggiero F (2005) The collagen superfamily: from the extracellular matrix to the cell membrane. Pathol Biol (Paris) 53:430–442

    CAS  Google Scholar 

  7. Gordon MK, Hahn RA (2010) Collagens. Cell Tissue Res 339:247–257

    CAS  PubMed Central  PubMed  Google Scholar 

  8. Eyre DR (1988) Collagens of the disc. In: Ghosh P (ed) The biology of intervertebral disc. CRC Press, Boca Raton, pp 171–188

    Google Scholar 

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

    CAS  PubMed Central  PubMed  Google Scholar 

  10. Eyre DR, Muir H (1977) Quantitative analysis of types I and II collagens in human intervertebral discs at various ages. Biochim Biophys Acta 492:29–42

    CAS  PubMed  Google Scholar 

  11. Roberts S, Menage J, Duance V, Volvo Award in basic sciences et al (1991) Collagen types around the cells of the intervertebral disc and cartilage end plate: an immunolocalization study. Spine (Phila Pa 1976) 16:1030–1038

    CAS  Google Scholar 

  12. Kempson GE, Muir H, Pollard C et al (1973) The tensile properties of the cartilage of human femoral condyles related to the content of collagen and glycosaminoglycans. Biochim Biophys Acta 297:456–472

    CAS  PubMed  Google Scholar 

  13. Schmidt MB, Mow VC, Chun LE et al (1990) Effects of proteoglycan extraction on the tensile behavior of articular cartilage. J Orthop Res 8:353–363

    CAS  PubMed  Google Scholar 

  14. Cole TC, Burkhardt D, Frost L et al (1985) The proteoglycans of the canine intervertebral disc. Biochim Biophys Acta 839:127–138

    CAS  PubMed  Google Scholar 

  15. McDevitt C, Billingham M, Muir H (1981) In vivo metabolism of proteoglycans in experimental osteoarthritic and normal canine articular cartilage and the intervertebral discs. Semin Arthritis Rheum 11:17–18

    CAS  Google Scholar 

  16. Oegema TR Jr, Bradford DS, Cooper KM (1979) Aggregated proteoglycan synthesis in organ cultures of human nucleus pulposus. J Biol Chem 254:10579–10581

    CAS  PubMed  Google Scholar 

  17. Venn G, Mason RM (1983) Biosynthesis and metabolism in vivo of intervertebral-disc proteoglycans in the mouse. Biochem J 215:217–225

    CAS  PubMed Central  PubMed  Google Scholar 

  18. DiFabio JL, Pearce RH, Caterson B et al (1987) The heterogeneity of the non-aggregating proteoglycans of the human intervertebral disc. Biochem J 244:27–33

    CAS  PubMed Central  PubMed  Google Scholar 

  19. Adams P, Muir H (1976) Qualitative changes with age of proteoglycans of human lumbar discs. Ann Rheum Dis 35:289–296

    CAS  PubMed Central  PubMed  Google Scholar 

  20. Johnstone B, Bayliss MT (1995) The large proteoglycans of the human intervertebral disc. Changes in their biosynthesis and structure with age, topography, and pathology. Spine (Phila Pa 1976) 20:674–684

    CAS  Google Scholar 

  21. Adams P, Eyre DR, Muir H (1977) Biochemical aspects of development and ageing of human lumbar intervertebral discs. Rheumatol Rehabil 16:22–29

    CAS  PubMed  Google Scholar 

  22. Urban J, Maroudas A (1980) The chemistry of the intervertebral disc in relation to its physiological function. Clin Rheum Dis 6:51–76

    Google Scholar 

  23. Hayes AJ, Isaacs MD, Hughes C et al (2011) Collagen fibrillogenesis in the development of the annulus fibrosus of the intervertebral disc. Eur Cell Mater 22:226–241

    CAS  PubMed  Google Scholar 

  24. Jahnke MR, McDevitt CA (1988) Proteoglycans of the human intervertebral disc. Electrophoretic heterogeneity of the aggregating proteoglycans of the nucleus pulposus. Biochem J 251:347–356

    CAS  PubMed Central  PubMed  Google Scholar 

  25. McDevitt C (1988) Proteoglycans of the intervertebral disc. In: Ghosh P (ed) The biology of the intervertebral disc. CRC Press, Boca Raton, pp 151–170

    Google Scholar 

  26. Bayliss MT, Johnstone B (1992) Biochemistry of the intervertebral disc. In: MIV J (ed) The Lumbar Spine and Back pain, 4th edn. Churchill Livingstone, London, pp 111–31

  27. Oegema TR Jr (1993) Biochemistry of the intervertebral disc. Clin Sports Med 12:419–439

    PubMed  Google Scholar 

  28. Roughley PJ, Melching LI, Heathfield TF et al (2006) The structure and degradation of aggrecan in human intervertebral disc. Eur Spine J 15(Suppl 3):S326–S332

    PubMed  Google Scholar 

  29. Sivan SS, Tsitron E, Wachtel E et al (2006) Aggrecan turnover in human intervertebral disc as determined by the racemization of aspartic acid. J Biol Chem 281:13009–13014

    CAS  PubMed  Google Scholar 

  30. Bushell GR, Ghosh P, Taylor TF et al (1977) Proteoglycan chemistry of the intervertebral disks. Clin Orthop Relat Res 129:115–123

    Google Scholar 

  31. Hayes AJ, Benjamin M, Ralphs JR (2001) Extracellular matrix in development of the intervertebral disc. Matrix Biol 20:107–121

    CAS  PubMed  Google Scholar 

  32. Hayes AJ, Hughes CE, Ralphs JR et al (2011) Chondroitin sulphate sulphation motif expression in the ontogeny of the intervertebral disc. Eur Cell Mater 21:1–14

    CAS  PubMed  Google Scholar 

  33. Caterson B (2012) Fell-Muir Lecture: chondroitin sulphate glycosaminoglycans: fun for some and confusion for others. Int J Exp Pathol 93:1–10

    CAS  PubMed Central  PubMed  Google Scholar 

  34. Pearce RH, Grimmer BJ (1976) The chemical constitution of the proteoglycan of human intervertebral disc. Biochem J 157:753–763

    CAS  PubMed Central  PubMed  Google Scholar 

  35. Antonopoulous C, L F, S G et al (1969) Fractionation of keratan sulphate from human nucleus pulposus. Acta Chem Scand 1:23

    Google Scholar 

  36. Choi HU, Meyer K (1975) The structure of keratan sulphates from various sources. Biochem J 151:543–553

    CAS  PubMed Central  PubMed  Google Scholar 

  37. Heinegard D, Axelsson I, Inerot S (1979) Skeletal keratan sulfate from different tissues. Characterization and alkaline degradation. Biochim Biophys Acta 581:122–127

    CAS  PubMed  Google Scholar 

  38. Eyre DR (1979) Biochemistry of the intervertebral disc. Int Rev Connect Tissue Res 8:227–291

    CAS  PubMed  Google Scholar 

  39. Scott JE, Bosworth TR, Cribb AM et al (1994) The chemical morphology of age-related changes in human intervertebral disc glycosaminoglycans from cervical, thoracic and lumbar nucleus pulposus and annulus fibrosus. J Anat 184(Pt 1):73–82

    PubMed Central  PubMed  Google Scholar 

  40. Melrose J, Smith S, Ghosh P et al (2003) Perlecan, the multidomain heparan sulfate proteoglycan of basement membranes, is also a prominent component of the cartilaginous primordia in the developing human fetal spine. J Histochem Cytochem 51:1331–1341

    CAS  PubMed  Google Scholar 

  41. Hardingham TE, Adams P (1976) A method for the determination of hyaluronate in the presence of other glycosaminoglycans and its application to human intervertebral disc. Biochem J 159:143–147

    CAS  PubMed Central  PubMed  Google Scholar 

  42. Inkinen RI, Lammi MJ, Agren U et al (1999) Hyaluronan distribution in the human and canine intervertebral disc and cartilage endplate. Histochem J 31:579–587

    CAS  PubMed  Google Scholar 

  43. Johnson EF, Caldwell RW, Berryman HE et al (1984) Elastic fibres in the annulus fibrosus of the dog intervertebral disc. Acta Anat 118:238–242

    CAS  PubMed  Google Scholar 

  44. Johnson EF, Chetty K, Moore IM et al (1982) The distribution and arrangement of elastic fibres in the intervertebral disc of the adult human. J Anat 135:301–309

    CAS  PubMed Central  PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  46. Ghosh P, Bushell GR, Taylor TF et al (1977) Collagens, elastin and noncollagenous protein of the intervertebral disk. Clin Orthop Relat Res 129:124–132

    Google Scholar 

  47. Yu J, Tirlapur U, Fairbank J et al (2007) Microfibrils, elastin fibres and collagen fibres in the human intervertebral disc and bovine tail disc. J Anat 210:460–471

    PubMed Central  PubMed  Google Scholar 

  48. Yu J, Winlove PC, Roberts S et al (2002) Elastic fibre organization in the intervertebral discs of the bovine tail. J Anat 201:465–475

    PubMed Central  PubMed  Google Scholar 

  49. Hayes AJ, Lord MS, Smith SM et al (2011) Colocalization in vivo and association in vitro of perlecan and elastin. Histochem Cell Biol 136:437–454

    CAS  PubMed  Google Scholar 

  50. Kielty CM, Sherratt MJ, Shuttleworth CA (2002) Elastic fibres. J Cell Sci 115:2817–2828

    CAS  PubMed  Google Scholar 

  51. Hynes RO, Yamada KM (1982) Fibronectins: multifunctional modular glycoproteins. J Cell Biol 95:369–377

    CAS  PubMed  Google Scholar 

  52. Anderson DG, Markova D, Adams SL et al (2010) Fibronectin splicing variants in human intervertebral disc and association with disc degeneration. Spine (Phila Pa 1976) 35:1581–1588

    Google Scholar 

  53. Chen J, Jing L, Gilchrist CL et al (2009) Expression of laminin isoforms, receptors, and binding proteins unique to nucleus pulposus cells of immature intervertebral disc. Connect Tissue Res 50:294–306

    PubMed Central  PubMed  Google Scholar 

  54. Hayes AJ, Smith SM, Gibson MA et al (2011) Comparative immunolocalization of the elastin fiber-associated proteins fibrillin-1, LTBP-2, and MAGP-1 with components of the collagenous and proteoglycan matrix of the fetal human intervertebral disc. Spine (Phila Pa 1976) 36:E1365–E1372

    Google Scholar 

  55. Li B, Urban JP, Yu J (2012) The distribution of fibrillin-2 and LTBP-2, and their co-localisation with fibrillin-1 in adult bovine tail disc. J Anat 220:164–172

    CAS  PubMed Central  PubMed  Google Scholar 

  56. Schumacher BL, Block JA, Schmid TM et al (1994) A novel proteoglycan synthesized and secreted by chondrocytes of the superficial zone of articular cartilage. Arch Biochem Biophys 311:144–152

    CAS  PubMed  Google Scholar 

  57. Shine KM, Simson JA, Spector M (2009) Lubricin distribution in the human intervertebral disc. J Bone Joint Surg Am 91:2205–2212

    PubMed  Google Scholar 

  58. Gruber HE, Ingram JA, Hanley EN, Jr (2006) Immunolocalization of thrombospondin in the human and sand rat intervertebral disc. Spine (Phila Pa 1976) 31:2556–2561

    Google Scholar 

  59. Ishii Y, Thomas AO, Guo XE et al (2006) Localization and distribution of cartilage oligomeric matrix protein in the rat intervertebral disc. Spine (Phila Pa 1976) 31:1539–1546

    Google Scholar 

  60. Gruber HE, Ingram JA, Hanley EN Jr (2002) Tenascin in the human intervertebral disc: alterations with aging and disc degeneration. Biotech Histochem 77:37–41

    CAS  PubMed  Google Scholar 

  61. Mort JS, Caterson B, Poole AR et al (1985) The origin of human cartilage proteoglycan link-protein heterogeneity and fragmentation during aging. Biochem J 232:805–812

    CAS  PubMed Central  PubMed  Google Scholar 

  62. Tengblad A, Pearce RH, Grimmer BJ (1984) Demonstration of link protein in proteoglycan aggregates from human intervertebral disc. Biochem J 222:85–92

    CAS  PubMed Central  PubMed  Google Scholar 

  63. Pearce RH, Mathieson JM, Mort JS et al (1989) Effect of age on the abundance and fragmentation of link protein of the human intervertebral disc. J Orthop Res 7:861–867

    CAS  PubMed  Google Scholar 

  64. Matsunaga S, Nagano S, Onishi T et al (2003) Age-related changes in expression of transforming growth factor-beta and receptors in cells of intervertebral discs. J Neurosurg 98:63–67

    CAS  PubMed  Google Scholar 

  65. Murakami H, Yoon ST, Attallah-Wasif ES et al (2006) The expression of anabolic cytokines in intervertebral discs in age-related degeneration. Spine (Phila Pa 1976) 31:1770–1774

    Google Scholar 

  66. Dahia CL, Mahoney EJ, Durrani AA et al (2009) Intercellular signaling pathways active during intervertebral disc growth, differentiation, and aging. Spine (Phila Pa 1976) 34:456–462

    Google Scholar 

  67. Kondo N, Yuasa T, Shimono K et al (2011) Intervertebral disc development is regulated by Wnt/beta-catenin signaling. Spine (Phila Pa 1976) 36:E513–E518

    Google Scholar 

  68. Hayes AJ, Benjamin M, Ralphs JR (1999) Role of actin stress fibres in the development of the intervertebral disc: cytoskeletal control of extracellular matrix assembly. Dev Dyn 215:179–189

    CAS  PubMed  Google Scholar 

  69. Weiler C, Nerlich AG, Zipperer J et al (2002) 2002 SSE Award Competition in Basic Science: expression of major matrix metalloproteinases is associated with intervertebral disc degradation and resorption. Eur Spine J 11:308–320

    CAS  PubMed Central  PubMed  Google Scholar 

  70. Murphy G, Nagase H (2011) Localizing matrix metalloproteinase activities in the pericellular environment. FEBS J 278:2–15

    CAS  PubMed Central  PubMed  Google Scholar 

  71. Primakoff P, Myles DG (2000) The ADAM gene family: surface proteins with adhesion and protease activity. Trends Genet 16:83–87

    CAS  PubMed  Google Scholar 

  72. Apte SS (2009) A disintegrin-like and metalloprotease (reprolysin-type) with thrombospondin type 1 motif (ADAMTS) superfamily: functions and mechanisms. J Biol Chem 284:31493–31497

    CAS  PubMed Central  PubMed  Google Scholar 

  73. Ariga K, Yonenobu K, Nakase T et al (2001) Localization of cathepsins D, K, and L in degenerated human intervertebral discs. Spine (Phila Pa 1976) 26:2666–2672

    CAS  Google Scholar 

  74. Melrose J, Ghosh P, Taylor TK (1987) Neutral proteinases of the human intervertebral disc. Biochim Biophys Acta 923:483–495

    CAS  PubMed  Google Scholar 

  75. Tiaden AN, Klawitter M, Lux V et al (2012) Detrimental role for human high temperature requirement serine protease A1 (HTRA1) in the pathogenesis of intervertebral disc (IVD) degeneration. J Biol Chem 287:21335–21345

    CAS  PubMed Central  PubMed  Google Scholar 

  76. Walter BA, Korecki CL, Purmessur D et al (2011) Complex loading affects intervertebral disc mechanics and biology. Osteoarthritis Cartilage 19:1011–1018

    CAS  PubMed Central  PubMed  Google Scholar 

  77. Le Maitre CL, Freemont AJ, Hoyland JA (2005) The role of interleukin-1 in the pathogenesis of human intervertebral disc degeneration. Arthritis Res Ther 7:R732–R737

    PubMed Central  PubMed  Google Scholar 

  78. Wang M, Tang D, Shu B et al (2012) Conditional activation of beta-catenin signaling in mice leads to severe defects in intervertebral disc tissue. Arthritis Rheum 64:2611–2623

    CAS  PubMed Central  PubMed  Google Scholar 

  79. Razaq MS (2002) The effect of extracellular pH on cartilage tissue metabolism and turnover. University of Oxford, Oxford

    Google Scholar 

  80. Nachemson A (1969) Intradiscal measurements of pH in patients with lumbar rhizopathies. Acta Orthop Scand 40:23–42

    CAS  PubMed  Google Scholar 

  81. Urban JP, Roberts S (2003) Degeneration of the intervertebral disc. Arthritis Res Ther 5:120–130

    PubMed Central  PubMed  Google Scholar 

  82. Sztrolovics R, White RJ, Poole AR et al (1999) Resistance of small leucine-rich repeat proteoglycans to proteolytic degradation during interleukin-1-stimulated cartilage catabolism. Biochem J 339(Pt 3):571–577

    CAS  PubMed Central  PubMed  Google Scholar 

  83. Roughley PJ, Alini M, Antoniou J (2002) The role of proteoglycans in aging, degeneration and repair of the intervertebral disc. Biochem Soc Trans 30:869–874

    CAS  PubMed  Google Scholar 

  84. Dickson IR, Happey F, Pearson CH et al (1967) Variations in the protein components of human intervertebral disk with age. Nature 215:52–53

    CAS  PubMed  Google Scholar 

  85. Banga I (1975) Investigations of fluorescent peptides and lipofuscins of human intervertebral disc relating to atherosclerosis. Atherosclerosis 22:533–541

    CAS  PubMed  Google Scholar 

  86. Roberts S, Caterson B, Evans H et al (1994) Proteoglycan components of the intervertebral disc and cartilage endplate: an immunolocalization study of animal and human tissues. Histochem J 26:402–411

    CAS  PubMed  Google Scholar 

  87. Inkinen RI, Lammi MJ, Lehmonen S et al (1998) Relative increase of biglycan and decorin and altered chondroitin sulfate epitopes in the degenerating human intervertebral disc. J Rheumatol 25:506–514

    CAS  PubMed  Google Scholar 

  88. Liu J, Roughley PJ, Mort JS (1991) Identification of human intervertebral disc stromelysin and its involvement in matrix degradation. J Orthop Res 9:568–575

    CAS  PubMed  Google Scholar 

  89. Crean JK, Roberts S, Jaffray DC et al (1997) Matrix metalloproteinases in the human intervertebral disc: role in disc degeneration and scoliosis. Spine (Phila Pa 1976) 22:2877–2884

    CAS  Google Scholar 

  90. Roberts S, Caterson B, Menage J et al (2000) Matrix metalloproteinases and aggrecanase: their role in disorders of the human intervertebral disc. Spine (Phila Pa 1976) 25:3005–3013

    CAS  Google Scholar 

  91. Le Maitre CL, Freemont AJ, Hoyland JA (2004) Localization of degradative enzymes and their inhibitors in the degenerate human intervertebral disc. J Pathol 204:47–54

    PubMed  Google Scholar 

  92. Pockert AJ, Richardson SM, Le Maitre CL et al (2009) Modified expression of the ADAMTS enzymes and tissue inhibitor of metalloproteinases 3 during human intervertebral disc degeneration. Arthritis Rheum 60:482–491

    CAS  PubMed  Google Scholar 

  93. Zhang Q, Huang M, Wang X et al (2012) Negative effects of ADAMTS-7 and ADAMTS-12 on endplate cartilage differentiation. J Orthop Res 30:1238–1243

    CAS  PubMed  Google Scholar 

  94. Goode AP, Marshall SW, Kraus VB et al (2012) Association between serum and urine biomarkers and lumbar spine individual radiographic features: the Johnston County Osteoarthritis Project. Osteoarthritis Cartilage 20:1286–1293

    CAS  PubMed Central  PubMed  Google Scholar 

  95. Melrose J, Smith SM, Fuller ES 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

    PubMed Central  PubMed  Google Scholar 

  96. Brown S, Melrose J, Caterson B et al (2012) A comparative evaluation of the small leucine-rich proteoglycans of pathological human intervertebral discs. Eur Spine J 21(Suppl 2):S154–S159

    PubMed  Google Scholar 

  97. Bada JL (1984) In vivo racemization in mammalian proteins. Methods Enzymol 106:98–115

    CAS  PubMed  Google Scholar 

  98. Helfman PM, Bada JL (1975) Aspartic acid racemization in tooth enamel from living humans. Proc Natl Acad Sci USA 72:2891–2894

    CAS  PubMed Central  PubMed  Google Scholar 

  99. Bada JL, Kvenvolden KA, Peterson ET (1973) Racemization of amino acids in bones. Nature 245:308–310

    Google Scholar 

  100. Man EH, Sandhouse ME, Burg J et al (1983) Accumulation of d-aspartic acid with age in the human brain. Science 220:1407–1408

    CAS  PubMed  Google Scholar 

  101. Powell JT, Vine N, Crossman M (1992) On the accumulation of D-aspartate in elastin and other proteins of the ageing aorta. Atherosclerosis 97:201–208

    CAS  PubMed  Google Scholar 

  102. Ritz S, Schutz HW (1993) Aspartic acid racemization in intervertebral discs as an aid to postmortem estimation of age at death. J Forensic Sci 38:633–640

    CAS  PubMed  Google Scholar 

  103. London IM, West R, Shemin D et al (1950) On the origin of bile pigment in normal man. J Biol Chem 184:351–358

    CAS  PubMed  Google Scholar 

  104. Sivan SS, Wachtel E, Tsitron E et al (2008) Collagen turnover in normal and degenerate human intervertebral discs as determined by the racemization of aspartic acid. J Biol Chem 283:8796–8801

    CAS  PubMed  Google Scholar 

  105. Sivan SS, Van El B, Merkher Y et al (2012) Longevity of elastin in human intervertebral disc as probed by the racemization of aspartic acid. Biochim Biophys Acta 1820(10):1671–1677

    Google Scholar 

  106. Maroudas A, Palla G, Gilav E (1992) Racemization of aspartic acid in human articular cartilage. Connect Tissue Res 28:161–169

    CAS  PubMed  Google Scholar 

  107. Arany S, Ohtani S, Yoshioka N et al (2004) Age estimation from aspartic acid racemization of root dentin by internal standard method. Forensic Sci Int 141:127–130

    CAS  PubMed  Google Scholar 

  108. Helfman PM, Bada JL (1976) Aspartic acid racemisation in dentine as a measure of ageing. Nature 262:279–281

    CAS  PubMed  Google Scholar 

  109. Rufai A, Benjamin M, Ralphs JR (1995) The development of fibrocartilage in the rat intervertebral disc. Anat Embryol (Berl) 192:53–62

    CAS  Google Scholar 

  110. Wu JJ, Weis MA, Kim LS et al (2009) Differences in chain usage and cross-linking specificities of cartilage type V/XI collagen isoforms with age and tissue. J Biol Chem 284:5539–5545

    CAS  PubMed Central  PubMed  Google Scholar 

  111. Nerlich AG, Schleicher ED, Boos N, Volvo Award winner in basic science studies (1997) Immunohistologic markers for age-related changes of human lumbar intervertebral discs. Spine (Phila Pa 1976) 22:2781–2795

    CAS  Google Scholar 

  112. Wu JJ, Eyre DR, Slayter HS (1987) Type VI collagen of the intervertebral disc. Biochemical and electron-microscopic characterization of the native protein. Biochem J 248:373–381

    CAS  PubMed Central  PubMed  Google Scholar 

  113. Boos N, Nerlich AG, Wiest I et al (1997) Immunolocalization of type X collagen in human lumbar intervertebral discs during ageing and degeneration. Histochem Cell Biol 108:471–480

    CAS  PubMed  Google Scholar 

  114. Wu JJ, Eyre DR (2003) Intervertebral disc collagen. Usage of the short form of the alpha1(IX) chain in bovine nucleus pulposus. J Biol Chem 278:24521–24525

    CAS  PubMed  Google Scholar 

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Acknowledgments

Authors would like to thank Dr. Michelle Kumin for her help and suggestions in writing this article. They are grateful to EA Kerr and J Menage for help in preparation of the manuscript. The research leading to these results has received funding from the European Community’s Seventh Framework Programme (FP7, 2007–2013) under grant agreement no. HEALTH-F2-2008-201626 (Genodisc) and FP7-People-2007-2-2-ERG (grant agreement 224834). A.M.S.S. and Y.M acknowledge support from the Charles W. McCutchen Foundation.

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Authors and Affiliations

  1. Department of Biomedical Engineering, Technion, Israel Institute of Technology, 32000, Haifa, Israel

    Sarit Sara Sivan, Yulia Merkher & Alice Maroudas

  2. School of Biosciences, Cardiff University, Cardiff, Wales, UK

    Anthony J. Hayes & Bruce Caterson

  3. Faculty of Chemistry, Weizmann Institute of Science, 76100, Rehovot, Israel

    Ellen Wachtel

  4. Robert Jones and Agnes Hunt Orthopaedic Hospital NHS Foundation Trust and ISTM, Keele University, Oswestry, Shropshire, SY10 7AG, UK

    Sharon Brown & Sally Roberts

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  1. Sarit Sara Sivan
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  2. Anthony J. Hayes
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Correspondence to Sarit Sara Sivan.

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Sivan, S.S., Hayes, A.J., Wachtel, E. et al. Biochemical composition and turnover of the extracellular matrix of the normal and degenerate intervertebral disc. Eur Spine J 23 (Suppl 3), 344–353 (2014). https://doi.org/10.1007/s00586-013-2767-8

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