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European Spine Journal
Published in: European Spine Journal 4/2007

01-04-2007 | Review

Biological treatment strategies for disc degeneration: potentials and shortcomings

Authors: Günther Paesold, Andreas G. Nerlich, Norbert Boos

Published in: European Spine Journal | Issue 4/2007

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Abstract

Recent advances in molecular biology, cell biology and material sciences have opened a new emerging field of techniques for the treatment of musculoskeletal disorders. These new treatment modalities aim for biological repair of the affected tissues by introducing cell-based tissue replacements, genetic modifications of resident cells or a combination thereof. So far, these techniques have been successfully applied to various tissues such as bone and cartilage. However, application of these treatment modalities to cure intervertebral disc degeneration is in its very early stages and mostly limited to experimental studies in vitro or in animal studies. We will discuss the potential and possible shortcomings of current approaches to biologically cure disc degeneration by gene therapy or tissue engineering. Despite the increasing number of studies examining the therapeutic potential of biological treatment strategies, a practicable solution to routinely cure disc degeneration might not be available in the near future. However, knowledge gained from these attempts might be applied in a foreseeable future to cure the low back pain that often accompanies disc degeneration and therefore be beneficial for the patient.
Literature
1.
Adachi N, Sato K, Usas A, Fu FH, Ochi M, Han CW, Niyibizi C, Huard J (2002) Muscle derived, cell based ex vivo gene therapy for treatment of full thickness articular cartilage defects. J Rheumatol 29:1920–1930PubMed
2.
Adams MA, Dolan P (2005) Spine biomechanics. J Biomech 38:1972–1983PubMed
3.
Adams MA, Freeman BJ, Morrison HP, Nelson IW, Dolan P (2000) Mechanical initiation of intervertebral disc degeneration. Spine 25:1625–1636PubMed
4.
Ahn SH, Cho YW, Ahn MW, Jang SH, Sohn YK, Kim HS (2002) mRNA expression of cytokines and chemokines in herniated lumbar intervertebral discs. Spine 27:911–917PubMed
5.
Akiyama H, Chaboissier MC, Martin JF, Schedl A, de Crombrugghe B (2002) The transcription factor Sox9 has essential roles in successive steps of the chondrocyte differentiation pathway and is required for expression of Sox5 and Sox6. Genes Dev 16:2813–2828PubMed
6.
Ala-Kokko L (2002) Genetic risk factors for lumbar disc disease. Ann Med 34:42–47PubMed
7.
Allan DB, Waddell G (1989) An historical perspective on low back pain and disability. Acta Orthop Scand 234(Suppl):1–23
8.
An HS, Takegami K, Kamada H, Nguyen CM, Thonar EJ, Singh K, Andersson GB, Masuda K (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 31–22
9.
An HS, Thonar EJ, Masuda K (2003) Biological repair of intervertebral disc. Spine 28:S86–92PubMed
10.
Anderson DG, Izzo MW, Hall DJ, Vaccaro AR, Hilibrand A, Arnold W, Tuan RS, Albert TJ (2002) Comparative gene expression profiling of normal and degenerative discs: analysis of a rabbit annular laceration model. Spine 27:1291–1296PubMed
11.
Antoniou J, Goudsouzian NM, Heathfield TF, Winterbottom N, Steffen T, Poole AR, Aebi M, Alini M (1996) The human lumbar endplate. Evidence of changes in biosynthesis and denaturation of the extracellular matrix with growth, maturation, aging, and degeneration. Spine 21:1153–1161PubMed
12.
Antoniou J, Steffen T, Nelson F, Winterbottom N, Hollander AP, Poole RA, Aebi M, Alini M (1996) The human lumbar intervertebral disc: evidence for changes in the biosynthesis and denaturation of the extracellular matrix with growth, maturation, ageing, and degeneration. J Clin Invest 98:996–1003PubMed
13.
Ariga K, Yonenobu K, Nakase T, Kaneko M, Okuda S, Uchiyama Y, Yoshikawa H (2001) Localization of cathepsins D, K, and L in degenerated human intervertebral discs. Spine 26:2666–2672PubMed
14.
Aydelotte MB, Kuettner KE (1988) Differences between sub-populations of cultured bovine articular chondrocytes. I. Morphology and cartilage matrix production. Connect Tissue Res 18:205–222PubMed
15.
Baffi MO, Slattery E, Sohn P, Moses HL, Chytil A, Serra R (2004) Conditional deletion of the TGF-beta type II receptor in Col2a expressing cells results in defects in the axial skeleton without alterations in chondrocyte differentiation or embryonic development of long bones. Dev Biol 276:124–142PubMed
16.
Bartels EM, Fairbank JC, Winlove CP, Urban JP (1998) Oxygen and lactate concentrations measured in vivo in the intervertebral discs of patients with scoliosis and back pain. Spine 23:1–7; discussion 8
17.
Battie MC, Videman T, Gibbons LE, Fisher LD, Manninen H, Gill K (1995) 1995 Volvo Award in clinical sciences. Determinants of lumbar disc degeneration. A study relating lifetime exposures and magnetic resonance imaging findings in identical twins. Spine 20:2601–2612PubMedCrossRef
18.
Bertram H, Kroeber M, Wang H, Unglaub F, Guehring T, Carstens C, Richter W (2005) Matrix-assisted cell transfer for intervertebral disc cell therapy. Biochem Biophys Res Commun 331:1185–1192PubMed
19.
Bianco P, Gehron Robey P (2000) Marrow stromal stem cells. J Clin Invest 105:1663–1668PubMed
20.
Bianco P, Riminucci M, Gronthos S, Robey PG (2001) Bone marrow stromal stem cells: nature, biology, and potential applications. Stem Cells 19:180–192PubMed
21.
Bibby SR, Urban JP (2004) Effect of nutrient deprivation on the viability of intervertebral disc cells. Eur Spine J 13:695–701PubMed
22.
Bijkerk C, Houwing-Duistermaat JJ, Valkenburg HA, Meulenbelt I, Hofman A, Breedveld FC, Pols HA, van Duijn CM, Slagboom PE (1999) Heritabilities of radiologic osteoarthritis in peripheral joints and of disc degeneration of the spine. Arthritis Rheum 42:1729–1735PubMed
23.
Boden SD, Davis DO, Dina TS, Patronas NJ, Wiesel SW (1990) Abnormal magnetic-resonance scans of the lumbar spine in asymptomatic subjects. A prospective investigation. J Bone Joint Surg Am 72:403–408PubMed
24.
Nerlich AG, Schaaf R, Walchli B, Boos N (2006) Temporo-spatial distribution of blood vessels in human lumbar intervertebral discs. Eur Spine J (in press)
25.
Boos N, Weissbach S, Rohrbach H, Weiler C, Spratt KF, Nerlich AG (2002) Classification of age-related changes in lumbar intervertebral discs: 2002 Volvo Award in basic science. Spine 27:2631–2644PubMed
26.
Buckwalter JA (1995) Aging and degeneration of the human intervertebral disc. Spine 20:1307–1314PubMed
27.
Burke JG, Watson RW, Conhyea D, McCormack D, Dowling FE, Walsh MG, Fitzpatrick JM (2003) Human nucleus pulposis can respond to a pro-inflammatory stimulus. Spine 28:2685–2693PubMed
28.
Burke JG, Watson RW, McCormack D, Dowling FE, Walsh MG, Fitzpatrick JM (2002) Intervertebral discs which cause low back pain secrete high levels of proinflammatory mediators. J Bone Joint Surg Br 84:196–201PubMed
29.
Carreon LY, Ito T, Yamada M, Uchiyama S, Takahashi HE (1997) Neovascularization induced by anulus and its inhibition by cartilage endplate. Its role in disc absorption. Spine 22:1429–1434; discussion 1446–1427
30.
Chelberg MK, Banks GM, Geiger DF, Oegema TR Jr (1995) Identification of heterogeneous cell populations in normal human intervertebral disc. J Anat 186(Pt 1):43–53PubMed
31.
Ching CT, Chow DH, Yao FY, Holmes AD (2003) The effect of cyclic compression on the mechanical properties of the inter-vertebral disc: an in vivo study in a rat tail model. Clin Biomech (Bristol Avon) 18:182–189
32.
Chow DH, Luk KD, Evans JH, Leong JC (1996) Effects of short anterior lumbar interbody fusion on biomechanics of neighboring unfused segments. Spine 21:549–555PubMed
33.
Coventry MB, Ghormley RK, Kernohan JW (1945) The intervertebral disc: Its microscopic anatomy and pathology. Part II. Changes in the intervertebral disc concomittant with age. J Bone Joint Surg Am 27A:233–247
34.
Crean JK, Roberts S, Jaffray DC, Eisenstein SM, Duance VC (1997) Matrix metalloproteinases in the human intervertebral disc: role in disc degeneration and scoliosis. Spine 22:2877–2884PubMed
35.
Crevensten G, Walsh AJ, Ananthakrishnan D, Page P, Wahba GM, Lotz JC, Berven S (2004) Intervertebral disc cell therapy for regeneration: mesenchymal stem cell implantation in rat intervertebral discs. Ann Biomed Eng 32:430–434PubMed
36.
Crock HV, Goldwasser M, Yoshizawa H (1988) Vascular anatomy related to the intervertebral disc. In: Gosh P (eds) The biology of the intervertebral disc. CRC Press, Boca Raton, pp 109–133
37.
Crock HV, Yoshizawa H (1976) The blood supply of the lumbar vertebral column. Clin Orthop 115:6–21PubMed
38.
Darling EM, Athanasiou KA (2003) Biomechanical strategies for articular cartilage regeneration. Ann Biomed Eng 31:1114–1124PubMed
39.
De Bari C, Dell’Accio F, Tylzanowski P, Luyten FP (2001) Multipotent mesenchymal stem cells from adult human synovial membrane. Arthritis Rheum 44:1928–1942PubMed
40.
Deiss LP, Galinka H, Berissi H, Cohen O, Kimchi A (1996) Cathepsin D protease mediates programmed cell death induced by interferon-gamma, Fas/APO-1 and TNF-alpha. Embo J 15:3861–3870PubMed
41.
Deyo RA, Bass JE (1989) Lifestyle and low-back pain. The influence of smoking and obesity. Spine 14:501–506PubMed
42.
Doege KJ, Coulter SN, Meek LM, Maslen K, Wood JG (1997) A human-specific polymorphism in the coding region of the aggrecan gene. Variable number of tandem repeats produce a range of core protein sizes in the general population. J Biol Chem 272:13974–13979PubMed
43.
Doita M, Kanatani T, Harada T, Mizuno K (1996) Immunohistologic study of the ruptured intervertebral disc of the lumbar spine. Spine 21:235–241PubMed
44.
Doita M, Kanatani T, Ozaki T, Matsui N, Kurosaka M, Yoshiya S (2001) Influence of macrophage infiltration of herniated disc tissue on the production of matrix metalloproteinases leading to disc resorption. Spine 26:1522–1527PubMed
45.
Ebisui C, Tsujinaka T, Morimoto T, Kan K, Iijima S, Yano M, Kominami E, Tanaka K, Monden M (1995) Interleukin-6 induces proteolysis by activating intracellular proteases (cathepsins B and L, proteasome) in C2C12 myotubes. Clin Sci (Lond) 89:431–439
46.
Elfering A, Semmer N, Birkhofer D, Zanetti M, Hodler J, Boos N (2002) Risk factors for lumbar disc degeneration: a 5-year prospective MRI study in asymptomatic individuals. Spine 27:125–134PubMed
47.
Elfering A, Semmer NK, Schade V, Grund S, Boos N (2002) Supportive colleague, unsupportive supervisor: the role of provider-specific constellations of social support at work in the development of low back pain. J Occup Health Psychol 7:130–140PubMed
48.
Evans CH, Robbins PD, Ghivizzani SC, Herndon JH, Kang R, Bahnson AB, Barranger JA, Elders EM, Gay S, Tomaino MM, Wasko MC, Watkins SC, Whiteside TL, Glorioso JC, Lotze MT, Wright TM (1996) Clinical trial to assess the safety, feasibility, and efficacy of transferring a potentially anti-arthritic cytokine gene to human joints with rheumatoid arthritis. Hum Gene Ther 7:1261–1280PubMed
49.
Eyre DR, Benya PD, Buckwalter J et al (1988) Basic science perspectives. In: Frymoyer JW, Gordon SL (eds) New perspectives on low back pain. American Academy Orthopaedic Surgeons, Park Ridge, IL, pp 147–214
50.
Fischer L, Boland G, Tuan RS (2002) Wnt-3A enhances bone morphogenetic protein-2-mediated chondrogenesis of murine C3H10T1/2 mesenchymal cells. J Biol Chem 277:30870–30878PubMed
51.
Freemont AJ, Jeziorska M, Hoyland JA, Rooney P, Kumar S (2002) Mast cells in the pathogenesis of chronic back pain: a hypothesis. J Pathol 197:281–285PubMed
52.
Freemont AJ, Watkins A, Le Maitre C, Baird P, Jeziorska M, Knight MT, Ross ER, O’Brien JP, Hoyland JA (2002) Nerve growth factor expression and innervation of the painful intervertebral disc. J Pathol 197:286–292PubMed
53.
Gafni Y, Turgeman G, Liebergal M, Pelled G, Gazit Z, Gazit D (2004) Stem cells as vehicles for orthopedic gene therapy. Gene Ther 11:417–426PubMed
54.
Ganey T, Libera J, Moos V, Alasevic O, Fritsch KG, Meisel HJ, Hutton WC (2003) Disc chondrocyte transplantation in a canine model: a treatment for degenerated or damaged intervertebral disc. Spine 28:2609–2620PubMed
55.
Ganey TM, Meisel HJ (2002) A potential role for cell-based therapeutics in the treatment of intervertebral disc herniation. Eur Spine J 11(Suppl 2):S206–S214PubMed
56.
Gardlik R, Palffy R, Hodosy J, Lukacs J, Turna J, Celec P (2005) Vectors and delivery systems in gene therapy. Med Sci Monit 11:RA110–RA121PubMed
57.
Gerber A, Welte T, Ansorge S, Buhling F (2000) Expression of cathepsins B and L in human lung epithelial cells is regulated by cytokines. Adv Exp Med Biol 477:287–292PubMed
58.
Gerber A, Wille A, Welte T, Ansorge S, Buhling F (2001) Interleukin-6 and transforming growth factor-beta 1 control expression of cathepsins B and L in human lung epithelial cells. J Interferon Cytokine Res 21:11–19PubMed
59.
Gigante A, Bevilacqua C, Pagnotta A, Manzotti S, Toesca A, Greco F (2003) Expression of NGF, Trka and p75 in human cartilage. Eur J Histochem 47:339–344PubMed
60.
Goupille P, Jayson MI, Valat JP, Freemont AJ (1998) Matrix metalloproteinases: the clue to intervertebral disc degeneration? Spine 23:1612–1626PubMed
61.
Gruber HE, Fisher EC Jr, Desai B, Stasky AA, Hoelscher G, Hanley EN Jr (1997) Human intervertebral disc cells from the annulus: three-dimensional culture in agarose or alginate and responsiveness to TGF-beta1. Exp Cell Res 235:13–21PubMed
62.
Gruber HE, Hanley EN Jr (1998) Analysis of aging and degeneration of the human intervertebral disc. Comparison of surgical specimens with normal controls. Spine 23:751–757PubMed
63.
Gruber HE, Hanley EN Jr (2003) Recent advances in disc cell biology. Spine 28:186–193PubMed
64.
Gruber HE, Johnson TL, Leslie K, Ingram JA, Martin D, Hoelscher G, Banks D, Phieffer L, Coldham G, Hanley EN Jr (2002) Autologous intervertebral disc cell implantation: a model using Psammomys obesus, the sand rat. Spine 27:1626–1633PubMed
65.
Gruber HE, Norton HJ, Hanley EN Jr (2000) Anti-apoptotic effects of IGF-1 and PDGF on human intervertebral disc cells in vitro. Spine 25:2153–2157PubMed
66.
Handa T, Ishihara H, Ohshima H, Osada R, Tsuji H, Obata K (1997) Effects of hydrostatic pressure on matrix synthesis and matrix metalloproteinase production in the human lumbar intervertebral disc. Spine 22:1085–1091PubMed
67.
Haro H, Kato T, Komori H, Osada M, Shinomiya K (2002) Vascular endothelial growth factor (VEGF)-induced angiogenesis in herniated disc resorption. J Orthop Res 20:409–415PubMed
68.
Hastreiter D, Ozuna RM, Spector M (2001) Regional variations in certain cellular characteristics in human lumbar intervertebral discs, including the presence of alpha-smooth muscle actin. J Orthop Res 19:597–604PubMed
69.
Heikkila JK, Koskenvuo M, Heliovaara M, Kurppa K, Riihimaki H, Heikkila K, Rita H, Videman T (1989) Genetic and environmental factors in sciatica. Evidence from a nationwide panel of 9365 adult twin pairs. Ann Med 21:393–398PubMed
70.
Heliovaara M (1989) Risk factors for low back pain and sciatica. Ann Med 21:257–264PubMed
71.
Hestbaek L, Iachine IA, Leboeuf-Yde C, Kyvik KO, Manniche C (2004) Heredity of low back pain in a young population: a classical twin study. Twin Res 7:16–26PubMed
72.
Hickey DG, Frenkel SR, Di Cesare PE (2003) Clinical applications of growth factors for articular cartilage repair. Am J Orthop 32:70–76PubMed
73.
74.
Hoffmann A, Czichos S, Kaps C, Bachner D, Mayer H, Kurkalli BG, Zilberman Y, Turgeman G, Pelled G, Gross G, Gazit D (2002) The T-box transcription factor Brachyury mediates cartilage development in mesenchymal stem cell line C3H10T1/2. J Cell Sci 115:769–781PubMed
75.
Holm S, Maroudas A, Urban JP, Selstam G, Nachemson A (1981) Nutrition of the intervertebral disc: solute transport and metabolism. Connect Tissue Res 8:101–119PubMedCrossRef
76.
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 26:2543–2549PubMed
77.
Horwitz EM, Gordon PL, Koo WK, Marx JC, Neel MD, McNall RY, Muul L, Hofmann T (2002) Isolated allogeneic bone marrow-derived mesenchymal cells engraft and stimulate growth in children with osteogenesis imperfecta: Implications for cell therapy of bone. Proc Natl Acad Sci USA 99:8932–8937PubMed
78.
Horwitz EM, Prockop DJ, Fitzpatrick LA, Koo WW, Gordon PL, Neel M, Sussman M, Orchard P, Marx JC, Pyeritz RE, Brenner MK (1999) Transplantability and therapeutic effects of bone marrow-derived mesenchymal cells in children with osteogenesis imperfecta. Nat Med 5:309–313PubMed
79.
Hutton WC, Ganey TM, Elmer WA, Kozlowska E, Ugbo JL, Doh ES, Whitesides TE Jr (2000) Does long-term compressive loading on the intervertebral disc cause degeneration? Spine 25:2993–3004PubMed
80.
Iatridis JC, Mente PL, Stokes IA, Aronsson DD, Alini M (1999) Compression-induced changes in intervertebral disc properties in a rat tail model. Spine 24:996–1002PubMed
81.
Ikehara S (2000) Pluripotent hemopoietic stem cells in mice and humans. Proc Soc Exp Biol Med 223:149–155PubMed
82.
Inoue H (1981) Three-dimensional architecture of lumbar intervertebral discs. Spine 6:139–146PubMed
83.
Jim JJ, Noponen-Hietala N, Cheung KM, Ott J, Karppinen J, Sahraravand A, Luk KD, Yip SP, Sham PC, Song YQ, Leong JC, Cheah KS, Ala-Kokko L, Chan D (2005) The TRP2 allele of COL9A2 is an age-dependent risk factor for the development and severity of intervertebral disc degeneration. Spine 30:2735–2742PubMed
84.
Jimbo K, Park JS, Yokosuka K, Sato K, Nagata K (2005) Positive feedback loop of interleukin-1beta upregulating production of inflammatory mediators in human intervertebral disc cells in vitro. J Neurosurg Spine 2:589–595PubMed
85.
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 42:197–207PubMed
86.
Johnson WE, Evans H, Menage J, Eisenstein SM, El Haj A, Roberts S (2001) Immunohistochemical detection of Schwann cells in innervated and vascularized human intervertebral discs. Spine 26:2550–2557PubMed
87.
Jones G, White C, Sambrook P, Eisman J (1998) Allelic variation in the vitamin D receptor, lifestyle factors and lumbar spinal degenerative disease. Ann Rheum Dis 57:94–99PubMedCrossRef
88.
Jullig M, Zhang WV, Stott NS (2004) Gene therapy in orthopaedic surgery: the current status. ANZ J Surg 74:46–54PubMed
89.
Kalajzic I, Stover ML, Liu P, Kalajzic Z, Rowe DW, Lichtler AC (2001) Use of VSV-G pseudotyped retroviral vectors to target murine osteoprogenitor cells. Virology 284:37–45PubMed
90.
Kanemoto M, Hukuda S, Komiya Y, Katsuura A, Nishioka J (1996) Immunohistochemical study of matrix metalloproteinase-3 and tissue inhibitor of metalloproteinase-1 human intervertebral discs. Spine 21:1–8PubMed
91.
Kang JD, Georgescu HI, McIntyre-Larkin L, Stefanovic-Racic M, Donaldson WF 3rd, Evans CH (1996) Herniated lumbar intervertebral discs spontaneously produce matrix metalloproteinases, nitric oxide, interleukin-6, and prostaglandin E2. Spine 21:271–277PubMed
92.
Kang JD, Stefanovic-Racic M, McIntyre LA, Georgescu HI, Evans CH (1997) Toward a biochemical understanding of human intervertebral disc degeneration and herniation. Contributions of nitric oxide, interleukins, prostaglandin E2, and matrix metalloproteinases. Spine 22:1065–1073PubMed
93.
Karppinen J, Paakko E, Paassilta P, Lohiniva J, Kurunlahti M, Tervonen O, Nieminen P, Goring HH, Malmivaara A, Vanharanta H, Ala-Kokko L (2003) Radiologic phenotypes in lumbar MR imaging for a gene defect in the COL9A3 gene of type IX collagen. Radiology 227:143–148PubMed
94.
Karppinen J, Paakko E, Raina S, Tervonen O, Kurunlahti M, Nieminen P, Ala-Kokko L, Malmivaara A, Vanharanta H (2002) Magnetic resonance imaging findings in relation to the COL9A2 tryptophan allele among patients with sciatica. Spine 27:78–83PubMed
95.
Kawaguchi Y, Kanamori M, Ishihara H, Ohmori K, Matsui H, Kimura T (2002) The association of lumbar disc disease with vitamin-D receptor gene polymorphism. J Bone Joint Surg Am 84-A:2022–2028PubMed
96.
Kawaguchi Y, Osada R, Kanamori M, Ishihara H, Ohmori K, Matsui H, Kimura T (1999) Association between an aggrecan gene polymorphism and lumbar disc degeneration. Spine 24:2456–2460PubMed
97.
Kawakami M, Matsumoto T, Hashizume H, Kuribayashi K, Chubinskaya S, Yoshida M (2005) Osteogenic protein-1 (osteogenic protein-1/bone morphogenetic protein-7) inhibits degeneration and pain-related behavior induced by chronically compressed nucleus pulposus in the rat. Spine 30:1933–1939PubMed
98.
Kay MA, Manno CS, Ragni MV, Larson PJ, Couto LB, McClelland A, Glader B, Chew AJ, Tai SJ, Herzog RW, Arruda V, Johnson F, Scallan C, Skarsgard E, Flake AW, High KA (2000) Evidence for gene transfer and expression of factor IX in haemophilia B patients treated with an AAV vector. Nat Genet 24:257–261PubMed
99.
Kim S, Le Visage C, Tateno K, Sieber A, Kostuik J, Leong K (2002) Interaction of human mesenchymal stem cells with disc cells: changes in biosynthesis of extracellular matrix. Spine J. 2:107S
100.
Kim YE, Goel VK, Weinstein JN, Lim TH (1991) Effect of disc degeneration at one level on the adjacent level in axial mode. Spine 16:331–335PubMed
101.
Klein RG, Eek BC, O’Neill CW, Elin C, Mooney V, Derby RR (2003) Biochemical injection treatment for discogenic low back pain: a pilot study. Spine J 3:220–226PubMed
102.
Koch H, Reinecke JA, Meijer H, Wehling P (1998) Spontaneous secretion of interleukin 1 receptor antagonist (IL-1ra) by cells isolated from herniated lumbar discal tissue after discectomy. Cytokine 10:703–705PubMed
103.
Konttinen YT, Kaapa E, Hukkanen M, Gu XH, Takagi M, Santavirta S, Alaranta H, Li TF, Suda A (1999) Cathepsin G in degenerating and healthy discal tissue. Clin Exp Rheumatol 17:197–204PubMed
104.
Konttinen YT, Kemppinen P, Li TF, Waris E, Pihlajamaki H, Sorsa T, Takagi M, Santavirta S, Schultz GS, Humphreys-Beher MG (1999) Transforming and epidermal growth factors in degenerated intervertebral discs. J Bone Joint Surg Br 81:1058–1063PubMed
105.
Kramer J, Hegert C, Guan K, Wobus AM, Muller PK, Rohwedel J (2000) Embryonic stem cell-derived chondrogenic differentiation in vitro: activation by BMP-2 and BMP-4. Mech Dev 92:193–205PubMed
106.
Kroeber MW, Unglaub F, Wang H, Schmid C, Thomsen M, Nerlich A, Richter W (2002) New in vivo animal model to create intervertebral disc degeneration and to investigate the effects of therapeutic strategies to stimulate disc regeneration. Spine 27:2684–2690PubMed
107.
Kuettner KE, Pauli BU, Gall G, Memoli VA, Schenk RK (1982) Synthesis of cartilage matrix by mammalian chondrocytes in vitro. I. Isolation, culture characteristics, and morphology. J Cell Biol 93:743–750PubMed
108.
Kuhlcke K, Fehse B, Schilz A, Loges S, Lindemann C, Ayuk F, Lehmann F, Stute N, Fauser AA, Zander AR, Eckert HG (2002) Highly efficient retroviral gene transfer based on centrifugation-mediated vector preloading of tissue culture vessels. Mol Ther 5:473–478PubMed
109.
Lattermann C, Oxner WM, Xiao X, Li J, Gilbertson LG, Robbins PD, Kang JD (2005) The adeno associated viral vector as a strategy for intradiscal gene transfer in immune competent and pre-exposed rabbits. Spine 30:497–504PubMed
110.
Le Blanc K, Tammik C, Rosendahl K, Zetterberg E, Ringden O (2003) HLA expression and immunologic properties of differentiated and undifferentiated mesenchymal stem cells. Exp Hematol 31:890–896PubMed
111.
Le Maitre CL, Freemont AJ, Hoyland JA (2004) Localization of degradative enzymes and their inhibitors in the degenerate human intervertebral disc. J Pathol 204:47–54PubMed
112.
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:R732–745PubMed
113.
Le Visage C, Tateno K, Sieber A, Kostuik J, Leong K (2003) Interaction of human mesenchymal stem cells with disc cells: changes in biosynthesis of extracellular matrix. In: 30th annual meeting. International Society for the Study of the Lumbar Spine
114.
Lee CK (1988) Accelerated degeneration of the segment adjacent to a lumbar fusion. Spine 13:375–377PubMed
115.
Legre J, Louis R, Serrano R, Debaene A (1979) Anatomo-radiological considerations about lumbar discography. An experimental study. Neuroradiology 17:77–82PubMed
116.
Li H, Zou X, Baatrup A, Lind M, Bunger C (2005) Cytokine profiles in conditioned media from cultured human intervertebral disc tissue. Implications of their effect on bone marrow stem cell metabolism. Acta Orthop 76:115–121PubMed
117.
Li S, Huang L (2000) Nonviral gene therapy: promises and challenges. Gene Ther 7:31–34PubMed
118.
Li S, Wu SP, Whitmore M, Loeffert EJ, Wang L, Watkins SC, Pitt BR, Huang L (1999) Effect of immune response on gene transfer to the lung via systemic administration of cationic lipidic vectors. Am J Physiol 276:L796–804PubMed
119.
Liu P, Kalajzic I, Stover ML, Rowe DW, Lichtler AC (2001) Human bone marrow stromal cells are efficiently transduced by vesicular stomatitis virus-pseudotyped retrovectors without affecting subsequent osteoblastic differentiation. Bone 29:331–335PubMed
120.
Livshits G, Cohen Z, Higla O, Yakovenko K (2001) Familial history, age and smoking are important risk factors for disc degeneration disease in Arabic pedigrees. Eur J Epidemiol 17:643–651PubMed
121.
Lotz JC, Chin JR (2000) Intervertebral disc cell death is dependent on the magnitude and duration of spinal loading. Spine 25:1477–1483PubMed
122.
Lotz JC, Colliou OK, Chin JR, Duncan NA, Liebenberg E (1998) Compression-induced degeneration of the intervertebral disc: an in vivo mouse model and finite-element study. Spine 23:2493–2506PubMed
123.
Luo J, Sun MH, Kang Q, Peng Y, Jiang W, Luu HH, Luo Q, Park JY, Li Y, Haydon RC, He TC (2005) Gene therapy for bone regeneration. Curr Gene Ther 5:167–179PubMed
124.
Lyons G, Eisenstein SM, Sweet MB (1981) Biochemical changes in intervertebral disc degeneration. Biochim Biophys Acta 673:443–453PubMed
125.
MacGregor AJ, Andrew T, Sambrook PN, Spector TD (2004) Structural, psychological, and genetic influences on low back and neck pain: a study of adult female twins. Arthritis Rheum 51:160–167PubMed
126.
Mahato RI, Kawabata K, Takakura Y, Hashida M (1995) In vivo disposition characteristics of plasmid DNA complexed with cationic liposomes. J Drug Target 3:149–157PubMed
127.
Maldonado BA, Oegema TR Jr (1992) Initial characterization of the metabolism of intervertebral disc cells encapsulated in microspheres. J Orthop Res 10:677–690PubMed
128.
Manno CS, Chew AJ, Hutchison S, Larson PJ, Herzog RW, Arruda VR, Tai SJ, Ragni MV, Thompson A, Ozelo M, Couto LB, Leonard DG, Johnson FA, McClelland A, Scallan C, Skarsgard E, Flake AW, Kay MA, High KA, Glader B (2003) AAV-mediated factor IX gene transfer to skeletal muscle in patients with severe hemophilia B. Blood 101:2963–2972PubMed
129.
Marchand F, Ahmed AM (1990) Investigation of the laminate structure of lumbar disc anulus fibrosus. Spine 15:402–410PubMed
130.
Maroon JC (2002) Current concepts in minimally invasive discectomy. Neurosurgery 51:137–145
131.
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 120:113–130PubMed
132.
Mason JM, Breitbart AS, Barcia M, Porti D, Pergolizzi RG, Grande DA (2000) Cartilage and bone regeneration using gene-enhanced tissue engineering. Clin Orthop Relat Res 379(Suppl):S171–S178PubMed
133.
Masuda K, Oegema TR Jr, An HS (2004) Growth factors and treatment of intervertebral disc degeneration. Spine 29:2757–2769PubMed
134.
Matsui H, Kanamori M, Ishihara H, Yudoh K, Naruse Y, Tsuji H (1998) Familial predisposition for lumbar degenerative disc disease. A case-control study. Spine 23:1029–1034PubMed
135.
Miyamoto H, Saura R, Harada T, Doita M, Mizuno K (2000) The role of cyclooxygenase-2 and inflammatory cytokines in pain induction of herniated lumbar intervertebral disc. Kobe J Med Sci 46:13–28PubMed
136.
Moon SH, Gilbertson LG, Nishida K, Knaub M, Muzzonigro T, Robbins PD, Evans CH, Kang JD (2000) Human intervertebral disc cells are genetically modifiable by adenovirus-mediated gene transfer: implications for the clinical management of intervertebral disc disorders. Spine 25:2573–2579PubMed
137.
Moon SH, Nishida K, Gilbertson L, Hall A, Robbins P, Kang JD (2001) Biologic response of human intervertebral disc cell to gene therapy cocktail. In: International Society for the Study of the Lumbar Spine. San Francisco, CA
138.
Nagase H, Okada Y (1997) Proteinases and matrix degeneration. In: Kelley W, Harris E, Ruddy S (eds) Rheumatology. WB Saunders, Philadelphia, pp 323–341
139.
Nemoto O, Yamagishi M, Yamada H, Kikuchi T, Takaishi H (1997) Matrix metalloproteinase-3 production by human degenerated intervertebral disc. J Spinal Disord 10:493–498PubMed
140.
Nerlich AG, Bachmeier BE, Boos N (2005) Expression of fibronectin and TGF-beta1 mRNA and protein suggest altered regulation of extracellular matrix in degenerated disc tissue. Eur Spine J 14:17–26PubMed
141.
Nishida K, Gilbertson LG, Robbins PD, Evans CH, Kang JD (2000) Potential applications of gene therapy to the treatment of intervertebral disc disorders. Clin Orthop Relat Res 379(Suppl):S234–S241PubMed
142.
Nishida K, Kang JD, Gilbertson LG, Moon SH, Suh JK, Vogt MT, Robbins PD, Evans CH (1999) 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. Spine 24:2419–2425PubMed
143.
Nishida T (1999) Kinetics of tissue and serum matrix metalloproteinase-3 and tissue inhibitor of metalloproteinases-1 in intervertebral disc degeneration and disc herniation. Kurume Med J 46:39–50PubMed
144.
Noponen-Hietala N, Kyllonen E, Mannikko M, Ilkko E, Karppinen J, Ott J, Ala-Kokko L (2003) Sequence variations in the collagen IX and XI genes are associated with degenerative lumbar spinal stenosis. Ann Rheum Dis 62:1208–1214PubMed
145.
Noponen-Hietala N, Virtanen I, Karttunen R, Schwenke S, Jakkula E, Li H, Merikivi R, Barral S, Ott J, Karppinen J, Ala-Kokko L (2005) Genetic variations in IL6 associate with intervertebral disc disease characterized by sciatica. Pain 114:186–194PubMed
146.
Nygaard OP, Mellgren SI, Osterud B (1997) The inflammatory properties of contained and noncontained lumbar disc herniation. Spine 22:2484–2488PubMed
147.
Ohshima H, Urban JP (1992) The effect of lactate and pH on proteoglycan and protein synthesis rates in the intervertebral disc. Spine 17:1079–1082PubMed
148.
Okuda S, Myoui A, Ariga K, Nakase T, Yonenobu K, Yoshikawa H (2001) Mechanisms of age-related decline in insulin-like growth factor-I dependent proteoglycan synthesis in rat intervertebral disc cells. Spine 26:2421–2426PubMed
149.
Osada R, Ohshima H, Ishihara H, Yudoh K, Sakai K, Matsui H, Tsuji H (1996) 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. J Orthop Res 14:690–699PubMed
150.
Ozaki S, Muro T, Ito S, Mizushima M (1999) Neovascularization of the outermost area of herniated lumbar intervertebral discs. J Orthop Sci 4:286–292PubMed
151.
Pai RR, D’sa B, Raghuveer CV, Kamath A (1999) Neovascularization of nucleus pulposus. A diagnostic feature of intervertebral disc prolapse. Spine 24:739–741PubMed
152.
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 25:679–689PubMed
153.
Paul R, Haydon RC, Cheng H, Ishikawa A, Nenadovich N, Jiang W, Zhou L, Breyer B, Feng T, Gupta P, He TC, Phillips FM (2003) Potential use of Sox9 gene therapy for intervertebral degenerative disc disease. Spine 28:755–763PubMed
154.
Pittenger MF, Mackay AM, Beck SC, Jaiswal RK, Douglas R, Mosca JD, Moorman MA, Simonetti DW, Craig S, Marshak DR (1999) Multilineage potential of adult human mesenchymal stem cells. Science 284:143–147PubMed
155.
Pluijm SM, van Essen HW, Bravenboer N, Uitterlinden AG, Smit JH, Pols HA, Lips P (2004) Collagen type I alpha1 Sp1 polymorphism, osteoporosis, and intervertebral disc degeneration in older men and women. Ann Rheum Dis 63:71–77PubMed
156.
Powell MC, Wilson M, Szypryt P, Symonds EM, Worthington BS (1986) Prevalence of lumbar disc degeneration observed by magnetic resonance in symptomless women. Lancet 2:1366–1367PubMed
157.
Puustjarvi K, Lammi M, Helminen H, Inkinen R, Tammi M (1994) Proteoglycans in the intervertebral disc of young dogs following strenuous running exercise. Connect Tissue Res 30:225–240PubMed
158.
Rainov NG (2000) A phase III clinical evaluation of herpes simplex virus type 1 thymidine kinase and ganciclovir gene therapy as an adjuvant to surgical resection and radiation in adults with previously untreated glioblastoma multiforme. Hum Gene Ther 11:2389–2401PubMed
159.
Rannou F, Lee TS, Zhou RH, Chin J, Lotz JC, Mayoux-Benhamou MA, Barbet JP, Chevrot A, Shyy JY (2004) Intervertebral disc degeneration: the role of the mitochondrial pathway in annulus fibrosus cell apoptosis induced by overload. Am J Pathol 164:915–924PubMed
160.
Reinecke JA, Wehling P, Robbins P, Evans CH, Sager M, Schulze-Allen G, Koch H (1997) [In vitro transfer of genes in spinal tissue]. Z Orthop Ihre Grenzgeb 135:412–416PubMedCrossRef
161.
Repanti M, Korovessis PG, Stamatakis MV, Spastris P, Kosti P (1998) Evolution of disc degeneration in lumbar spine: a comparative histological study between herniated and postmortem retrieved disc specimens. J Spinal Disord 11:41–45PubMed
162.
Richardson SM, Walker RV, Parker S, Rhodes NP, Hunt JA, Freemont AJ, Hoyland JA (2005) Intervertebral Disc Cell Mediated Mesenchymal Stem Cell Differentiation. Stem Cells 24:707–716PubMed
163.
Risbud MV, Izzo MW, Adams CS, al. e (2003) Mesenchymal stem cells respond to their microenvironment in vitro to assume nucleus pulposus-like phenotype. In: 30th annual meeting. International Society for the Study of the Lumbar Spine
164.
Ritter T, Lehmann M, Volk HD (2002) Improvements in gene therapy: averting the immune response to adenoviral vectors. Biodrugs 16:3–10PubMed
165.
Roberts S, Caterson B, Menage J, Evans EH, Jaffray DC, Eisenstein SM (2000) Matrix metalloproteinases and aggrecanase: their role in disorders of the human intervertebral disc. Spine 25:3005–3013PubMed
166.
Roberts S, Menage J, Duance V, Wotton S, Ayad S (1991) 1991 Volvo Award in basic sciences. Collagen types around the cells of the intervertebral disc and cartilage end plate: an immunolocalization study. Spine 16:1030–1038PubMed
167.
Roberts S, Menage J, Eisenstein SM (1993) The cartilage end-plate and intervertebral disc in scoliosis: calcification and other sequelae. J Orthop Res 11:747–757PubMed
168.
Romero NB, Benveniste O, Payan C, Braun S, Squiban P, Herson S, Fardeau M (2002) Current protocol of a research phase I clinical trial of full-length dystrophin plasmid DNA in Duchenne/Becker muscular dystrophies. Part II: clinical protocol. Neuromuscul Disord 12(Suppl 1):S45–48PubMed
169.
Saal JS, Franson RC, Dobrow R, Saal JA, White AH, Goldthwaite N (1990) High levels of inflammatory phospholipase A2 activity in lumbar disc herniations. Spine 15:674–678PubMed
170.
Sakai D, Mochida J, Iwashina T, Hiyama A, Omi H, Imai M, Nakai T, Ando K, Hotta T (2006) Regenerative effects of transplanting mesenchymal stem cells embedded in atelocollagen to the degenerated intervertebral disc. Biomaterials 27:335–345PubMed
171.
Sakai D, Mochida J, Iwashina T, Watanabe T, Nakai T, Ando K, Hotta T (2005) Differentiation of mesenchymal stem cells transplanted to a rabbit degenerative disc model: potential and limitations for stem cell therapy in disc regeneration. Spine 30:2379–2387PubMed
172.
Sakai D, Mochida J, Yamamoto Y, Nomura T, Okuma M, Nishimura K, Nakai T, Ando K, Hotta T (2003) Transplantation of mesenchymal stem cells embedded in Atelocollagen gel to the intervertebral disc: a potential therapeutic model for disc degeneration. Biomaterials 24:3531–3541PubMed
173.
Sambrook PN, MacGregor AJ, Spector TD (1999) Genetic influences on cervical and lumbar disc degeneration: a magnetic resonance imaging study in twins. Arthritis Rheum 42:366–372PubMed
174.
Sandover J (1983) Dynamic loading as a possible source of low-back disorders. Spine 8:652–658PubMed
175.
Sato M, Asazuma T, Ishihara M, Kikuchi T, Kikuchi M, Fujikawa K (2003) An experimental study of the regeneration of the intervertebral disc with an allograft of cultured annulus fibrosus cells using a tissue-engineering method. Spine 28:548–553PubMed
176.
Sato M, Asazuma T, Ishihara M, Kikuchi T, Masuoka K, Ichimura S, Kikuchi M, Kurita A, Fujikawa K (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 64A:248–256
177.
Sato M, Kikuchi M, Ishihara M, Asazuma T, Kikuchi T, Masuoka K, Hattori H, Fujikawa K (2003) Tissue engineering of the intervertebral disc with cultured annulus fibrosus cells using atelocollagen honeycomb-shaped scaffold with a membrane seal (ACHMS scaffold). Med Biol Eng Comput 41:365–371PubMed
178.
Scapinelli R (1993) Lumbar disc herniation in eight siblings with a positive family history for disc disease. Acta Orthop Belg 59:371–376PubMed
179.
Seki S, Kawaguchi Y, Chiba K, Mikami Y, Kizawa H, Oya T, Mio F, Mori M, Miyamoto Y, Masuda I, Tsunoda T, Kamata M, Kubo T, Toyama Y, Kimura T, Nakamura Y, Ikegawa S (2005) A functional SNP in CILP, encoding cartilage intermediate layer protein, is associated with susceptibility to lumbar disc disease. Nat Genet 37:607–612PubMed
180.
Shen B, Melrose J, Ghosh P, Taylor F (2003) Induction of matrix metalloproteinase-2 and -3 activity in ovine nucleus pulposus cells grown in three-dimensional agarose gel culture by interleukin-1beta: a potential pathway of disc degeneration. Eur Spine J 12:66–75PubMed
181.
Shieh SJ, Vacanti JP (2005) State-of-the-art tissue engineering: from tissue engineering to organ building. Surgery 137:1–7PubMed
182.
Sobajima S, Vadala G, Niyibizi C, al. e (2003) Stem cell therapy for degenerative disc disease: An in-vitro feasibility study. In: 30th annual meeting. International Society for the Study of the Lumbar Spine
183.
Solovieva S, Kouhia S, Leino-Arjas P, Ala-Kokko L, Luoma K, Raininko R, Saarela J, Riihimaki H (2004) Interleukin 1 polymorphisms and intervertebral disc degeneration. Epidemiology 15:626–633PubMed
184.
Solovieva S, Leino-Arjas P, Saarela J, Luoma K, Raininko R, Riihimaki H (2004) Possible association of interleukin 1 gene locus polymorphisms with low back pain. Pain 109:8–19PubMed
185.
Solovieva S, Lohiniva J, Leino-Arjas P, Raininko R, Luoma K, Ala-Kokko L, Riihimaki H (2002) COL9A3 gene polymorphism and obesity in intervertebral disc degeneration of the lumbar spine: evidence of gene-environment interaction. Spine 27:2691–2696PubMed
186.
Somia N, Verma IM (2000) Gene therapy: trials and tribulations. Nat Rev Genet 1:91–99PubMed
187.
Specchia N, Pagnotta A, Toesca A, Greco F (2002) Cytokines and growth factors in the protruded intervertebral disc of the lumbar spine. Eur Spine J 11:145–151PubMed
188.
Stabler A, Weiss M, Scheidler J, Krodel A, Seiderer M, Reiser M (1996) Degenerative disk vascularization on MRI: correlation with clinical and histopathologic findings. Skelet Radiol 25:119–126
189.
Stamenkovic I (2000) Matrix metalloproteinases in tumor invasion and metastasis. Semin Cancer Biol 10:415–433PubMed
190.
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 23:403–411PubMed
191.
Sztrolovics R, Alini M, Roughley PJ, Mort JS (1997) Aggrecan degradation in human intervertebral disc and articular cartilage. Biochem J 326(Pt 1):235–241PubMed
192.
Takahashi H, Suguro T, Okazima Y, Motegi M, Okada Y, Kakiuchi T (1996) Inflammatory cytokines in the herniated disc of the lumbar spine. Spine 21:218–224PubMed
193.
Takahashi M, Haro H, Wakabayashi Y, Kawa-uchi T, Komori H, Shinomiya K (2001) The association of degeneration of the intervertebral disc with 5a/6a polymorphism in the promoter of the human matrix metalloproteinase-3 gene. J Bone Joint Surg Br 83:491–495PubMed
194.
Takegami K, Masuda K, An H (2000) In vivo administration of osteogenic protein-1 increases proteoglycan content and disc height in rabbit intervertebral disc. Orthop Res Soc Trans 25:338
195.
Thompson JP, Oegema TR Jr, Bradford DS (1991) Stimulation of mature canine intervertebral disc by growth factors. Spine 16:253–260PubMed
196.
Tolonen J, Gronblad M, Vanharanta H, Virri J, Guyer RD, Rytomaa T, Karaharju EO (2005) Growth factor expression in degenerated intervertebral disc tissue An immunohistochemical analysis of transforming growth factor beta, fibroblast growth factor and platelet-derived growth factor. Eur Spine J 15:588–596PubMed
197.
Tolonen J, Gronblad M, Virri J, Seitsalo S, Rytomaa T, Karaharju E (1995) Basic fibroblast growth factor immunoreactivity in blood vessels and cells of disc herniations. Spine 20:271–276PubMed
198.
Tolonen J, Gronblad M, Virri J, Seitsalo S, Rytomaa T, Karaharju E (2001) Transforming growth factor beta receptor induction in herniated intervertebral disc tissue: an immunohistochemical study. Eur Spine J 10:172–176PubMed
199.
Trout JJ, Buckwalter JA, Moore KC (1982) Ultrastructure of the human intervertebral disc: II. Cells of the nucleus pulposus. Anat Rec 204:307–314PubMed
200.
Tsujinaka T, Kishibuchi M, Yano M, Morimoto T, Ebisui C, Fujita J, Ogawa A, Shiozaki H, Kominami E, Monden M (1997) Involvement of interleukin-6 in activation of lysosomal cathepsin and atrophy of muscle fibers induced by intramuscular injection of turpentine oil in mice. J Biochem (Tokyo) 122:595–600
201.
Tsuru M, Nagata K, Ueno T, Jimi A, Irie K, Yamada A, Nishida T, Sata M (2001) Electron microscopic observation of established chondrocytes derived from human intervertebral disc hernia (KTN-1) and role of macrophages in spontaneous regression of degenerated tissues. Spine J 1:422–431PubMed
202.
Urban JP, Holm S, Maroudas A (1978) Diffusion of small solutes into the intervertebral disc: as in vivo study. Biorheology 15:203–221PubMed
203.
Varlotta GP, Brown MD, Kelsey JL, Golden AL (1991) Familial predisposition for herniation of a lumbar disc in patients who are less than twenty-one years old. J Bone Joint Surg Am 73:124–128PubMed
204.
Vernon-Roberts B (1992) Age-related and degenerative pathology of intervertebral discs and apophyseal joints. In: Jayson MI (ed) The lumbar spine and back pain. Churchill Livingstone, Edinburh, pp 17–41
205.
Vernon-Roberts B (1988) Disc pathology and disease states. In: Gosh P (ed) The biology of the intervertebral disc. CRC Press, Boca Raton, Florida, pp 73–119
206.
Videman T, Battie MC (1999) The influence of occupation on lumbar degeneration. Spine 24:1164–1168PubMed
207.
Videman T, Gibbons LE, Battie MC, Maravilla K, Vanninen E, Leppavuori J, Kaprio J, Peltonen L (2001) The relative roles of intragenic polymorphisms of the vitamin d receptor gene in lumbar spine degeneration and bone density. Spine 26:E7–E12PubMed
208.
Videman T, Leppavuori J, Kaprio J, Battie MC, Gibbons LE, Peltonen L, Koskenvuo M (1998) Intragenic polymorphisms of the vitamin D receptor gene associated with intervertebral disc degeneration. Spine 23:2477–2485PubMed
209.
Wallach CJ, Sobajima S, Watanabe Y, Kim JS, Georgescu HI, Robbins P, Gilbertson LG, Kang JD (2003) Gene transfer of the catabolic inhibitor TIMP-1 increases measured proteoglycans in cells from degenerated human intervertebral discs. Spine 28:2331–2337PubMed
210.
Walmsley R (1953) The development and growth of the intervertebral disc. Edinburgh Med J 60:341–364PubMed
211.
Wang F, Duan R, Chirgwin J, Safe SH (2000) Transcriptional activation of cathepsin D gene expression by growth factors. J Mol Endocrinol 24:193–202PubMed
212.
Wehling P, Schulitz KP, Robbins PD, Evans CH, Reinecke JA (1997) Transfer of genes to chondrocytic cells of the lumbar spine. Proposal for a treatment strategy of spinal disorders by local gene therapy. Spine 22:1092–1097PubMed
213.
Weiler C, Nerlich AG, Bachmeier BE, Boos N (2005) Expression and distribution of tumor necrosis factor alpha in human lumbar intervertebral discs: a study in surgical specimen and autopsy controls. Spine 30:44–53; discussion 54
214.
Weiler C, Nerlich AG, Zipperer J, Bachmeier BE, Boos N (2002) 2002 SSE Award Competition in Basic Science: expression of major matrix metalloproteinases is associated with intervertebral disc degradation and resorption. Eur Spine J 11:308–320PubMed
215.
Weishaupt D, Zanetti M, Hodler J, Boos N (1998) MR imaging of the lumbar spine: prevalence of intervertebral disk extrusion and sequestration, nerve root compression, end plate abnormalities, and osteoarthritis of the facet joints in asymptomatic volunteers. Radiology 209:661–666PubMed
216.
Wolff JA, Malone RW, Williams P, Chong W, Acsadi G, Jani A, Felgner PL (1990) Direct gene transfer into mouse muscle in vivo. Science 247:1465–1468PubMed
217.
Yamazaki S, Banes AJ, Weinhold PS, Tsuzaki M, Kawakami M, Minchew JT (2002) Vibratory loading decreases extracellular matrix and matrix metalloproteinase gene expression in rabbit annulus cells. Spine J 2:415–420PubMed
218.
Yang NS, Burkholder J, Roberts B, Martinell B, McCabe D (1990) In vivo and in vitro gene transfer to mammalian somatic cells by particle bombardment. Proc Natl Acad Sci USA 87:9568–9572PubMed
219.
Yoon ST, Park JS, Kim KS, Li J, Attallah-Wasif ES, Hutton WC, Boden SD (2004) ISSLS prize winner: LMP-1 upregulates intervertebral disc cell production of proteoglycans and BMPs in vitro and in vivo. Spine 29:2603–2611PubMed
220.
Young HE, Steele TA, Bray RA, Hudson J, Floyd JA, Hawkins K, Thomas K, Austin T, Edwards C, Cuzzourt J, Duenzl M, Lucas PA, Black AC Jr (2001) Human reserve pluripotent mesenchymal stem cells are present in the connective tissues of skeletal muscle and dermis derived from fetal, adult, and geriatric donors. Anat Rec 264:51–62PubMed
221.
Yu J (2002) Elastic tissues of the intervertebral disc. Biochem Soc Trans 30:848–852PubMed
222.
Yu J, Winlove PC, Roberts S, Urban JP (2002) Elastic fibre organization in the intervertebral discs of the bovine tail. J Anat 201:465–475PubMed
223.
Zhang YG, Guo X, Xu P, Kang LL, Li J (2005) Bone mesenchymal stem cells transplanted into rabbit intervertebral discs can increase proteoglycans. Clin Orthop Relat Res 430:219–226PubMed
Metadata
Title
Biological treatment strategies for disc degeneration: potentials and shortcomings
Authors
Günther Paesold
Andreas G. Nerlich
Norbert Boos
Publication date
01-04-2007
Publisher
Springer-Verlag
Published in
European Spine Journal / Issue 4/2007
Print ISSN: 0940-6719
Electronic ISSN: 1432-0932
DOI
https://doi.org/10.1007/s00586-006-0220-y

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