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01-01-2008 | Review

Are animal models useful for studying human disc disorders/degeneration?

Authors: Mauro Alini, Stephen M. Eisenstein, Keita Ito, Christopher Little, A. Annette Kettler, Koichi Masuda, James Melrose, Jim Ralphs, Ian Stokes, Hans Joachim Wilke

Published in: European Spine Journal | Issue 1/2008

Abstract

Intervertebral disc (IVD) degeneration is an often investigated pathophysiological condition because of its implication in causing low back pain. As human material for such studies is difficult to obtain because of ethical and government regulatory restriction, animal tissue, organs and in vivo models have often been used for this purpose. However, there are many differences in cell population, tissue composition, disc and spine anatomy, development, physiology and mechanical properties, between animal species and human. Both naturally occurring and induced degenerative changes may differ significantly from those seen in humans. This paper reviews the many animal models developed for the study of IVD degeneration aetiopathogenesis and treatments thereof. In particular, the limitations and relevance of these models to the human condition are examined, and some general consensus guidelines are presented. Although animal models are invaluable to increase our understanding of disc biology, because of the differences between species, care must be taken when used to study human disc degeneration and much more effort is needed to facilitate research on human disc material.

Adams MA, Roughley PJ (2006) What is intervertebral disc degeneration, and what causes it? Spine 31:2151–2161PubMed

Aguiar DJ, Johnson SL, Oegema TR (1999) Notochordal cells interact with nucleus pulposus cells: regulation of proteoglycan synthesis. Exp Cell Res 246:129–137PubMed

Anderson GD, Li X, Tannoury T, Beck G, Balian G (2003) A fibronectin fragment stimulates intervertebral disc degeneration in vivo. Spine 28:2338–2345

Ando T, Kato F, Mimatsu K, Iwata H (1995) Effects of chondroitinase ABC on degenerative intervertebral discs. Clin Orthop Relat Res 318:214–221

Ariga K, Miyamoto S, Nakase T, Okuda S, Meng WX, Yonenobu K, Yoshikawa H (2001) The relationship between apoptosis of endplate chondrocytes and aging and degeneration of the intervertebral disc. Spine 26:2414–2420PubMed

Ariga K, Yonenobu K, Nakase T, Hosono N, Okuda S, Meng WX, Tamura Y, Yoshikawa H (2003) Mechanical stress-induced apoptosis of endplate chondrocytes in organ-cultured mouse intervertebral discs—an ex vivo study. Spine 28:1528–1533PubMed

Aszodi A, Chan D, Hunziker E, Bateman JF, Fassler R (1998) Collagen II is essential for the removal of the notochord and the formation of intervertebral discs. J Cell Biol 143:1399–1412PubMed

Bailey AS, Adler F, Min LS, Asher MA (2001) A comparison between bipedal and quadrupedal rats: do bipedal rats actually assume an upright posture? Spine 26:E308–E313PubMed

Barry FP, Neame PJ, Sasse J, Pearson D (1994) Length variation in the keratan sulfate domain of mammalian aggrecan. Matrix Biol 14:323–328PubMed

10.

Battie MC, Videman T, Parent E (2004) Lumbar disc degeneration: epidemiology and genetic influences. Spine 29:2679–2690PubMed

11.

Bayliss MT, Johnstone B, O’Brien JP (1988) 1988 Volvo award in basic science. Proteoglycan synthesis in the human intervertebral disc. Variation with age, region and pathology. Spine 13:972–981PubMed

12.

Behrens A, Haigh J, Mechta-Grigoriou F, Nagy A, Yaniv M, Wagner EF (2003) Impaired intervertebral disc formation in the absence of Jun. Development 130:103–109PubMed

13.

Benneker LM, Heini PF, Alini M, Anderson SE, Ito K (2005) 2004 Young Investigator Award Winner: vertebral endplate marrow contact channel occlusions and intervertebral disc degeneration. Spine 30:167–173PubMed

14.

Bernick S, Cailliet R (1982) Vertebral end-plate changes with aging of human vertebrae. Spine 7:97–102PubMed

15.

Berry RJ (1960) Genetical studies on the skeleton of the mouse 26. Pintail. Genet Res 1:439–451CrossRef

16.

Boszczyk BM, Boszczyk AA, Putz R (2001) Comparative and functional anatomy of the mammalian lumbar spine. Anat Rec 264:157–168PubMed

17.

Braund KG (1974) Some aspects of structure and function of the canine intervertebral disc. Ph.D. thesis, University of Sydney

18.

Bruehlmann SB, Matyas JR, Duncan NA (2004) ISSLS prize winner: collagen fibril sliding governs cell mechanics in the anulus fibrosus: an in situ confocal microscopy study of bovine discs. Spine 29:2612–2620PubMed

19.

Bushell GR, Ghosh DP, Taylor TK, Sutherland JM, Braund KG (1978) The effect of spinal fusion on the collagen and proteoglycans of the canine intervertebral disc. J Surg Res 25:61–69PubMed

20.

Bushell GR, Ghosh P, Taylor TK, Sutherland JM (1979) The collagen of the intervertebral disc in adolescent idiopathic scoliosis. J Bone Joint Surg Br 61-B:501–508PubMed

21.

Butler WF (1988) Comparative anatomy and development of the mammalian disc. In: Ghosh P (eds) The biology of the intervertebral disc. CRC, Boca Raton, FL, pp 83–108

22.

Cassidy JD, Yong-Hing K, Kirkaldy-Willis WH, Wilkinson AA (1988) A study of the effects of bipedism and upright posture on the lumbosacral spine and paravertebral muscles of the Wistar rat. Spine 13:301–308PubMed

23.

Cheung KM, Lu DS, Poon AM, Wang T, Luk KD, Leong JC (2003) Effect of melatonin suppression on scoliosis development in chickens by either constant light or surgical pinealectomy. Spine 28:1941–1944PubMed

24.

Cheung KM, Wang T, Poon AM, Carl A, Tranmer B, Hu Y, Luk KD, Leong JC (2005) The effect of pinealectomy on scoliosis development in young nonhuman primates. Spine 30:2009–2013PubMed

25.

Chiba K, Andersson GB, Masuda K, Momohara S, Williams JM, Thonar EJ (1998) A new culture system to study the metabolism of the intervertebral disc in vitro. Spine 23:1821–1827PubMed

26.

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 18:182–189

27.

Ching CT, Chow DH, Yao FY, Holmes AD (2004) Changes in nuclear composition following cyclic compression of the intervertebral disc in an in vivo rat-tail model. Med Eng Phys 26:587–594PubMed

28.

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

29.

Cole TC, Burkhardt D, Ghosh P, Ryan M, Taylor T (1985) Effects of spinal fusion on the proteoglycans of the canine intervertebral disc. J Orthop Res 3:277–291PubMed

30.

Cole TC, Ghosh P, Hannan NJ, Taylor TK, Bellenger CR (1987) The response of the canine intervertebral disc to immobilization produced by spinal arthrodesis is dependent on constitutional factors. J Orthop Res 5:337–347PubMed

31.

Cole TC, Ghosh P, Taylor TK (1986) Variations of the proteoglycans of the canine intervertebral disc with ageing. Biochim Biophys Acta 880:209–219PubMed

32.

Court C, Colliou OK, Chin JR, Liebenberg E, Bradford DS, Lotz JC (2001) The effect of static in vivo bending on the murine intervertebral disc. Spine J 1:239–245PubMed

33.

Demers CN, Antoniou J, Mwale F (2004) Value and limitations of using the bovine tail as a model for the human lumbar spine. Spine 29:2793–2799PubMed

34.

Elliott DM, Sarver JJ (2004) Young investigator award winner: validation of the mouse and rat disc as mechanical models of the human lumbar disc. Spine 29:713–722PubMed

35.

Fazzalari NL, Costi JJ, Hearn TC, Fraser RD, Vernon-Roberts B, Hutchinson J, Manthey BA, Parkinson IH, Sinclair C (2001) Mechanical and pathologic consequences of induced concentric anular tears in an ovine model. Spine 26:2575–2581PubMed

36.

Flannery CR, Little CB, Caterson B (1998) Molecular cloning and sequence analysis of the aggrecan interglobular domain from porcine, equine, bovine and ovine cartilage: comparison of proteinase-susceptible regions and sites of keratan sulfate substitution. Matrix Biol 16:507–511PubMed

37.

Foster MR, Allen MJ, Schoonmaker JE, Yuan HA, Kanazawa A, Park SA, Liu B (2002) Characterization of a developing lumbar arthrodesis in a sheep model with quantitative instability. Spine J 2:244–250PubMed

38.

Furuya S, Ohtsuki T, Yabe Y, Hosoda Y (2000) Ultrastructural study on calcification of cartilage: comparing ICR and twy mice. J Bone Miner Metab 18:140–147PubMed

39.

Gantenbein B, Grünhagen T, Lee CR, van Donkelaar CC, Alini M, Ito K (2006) An in vitro organ culturing system for intervertebral disc explants with vertebral endplates: a feasibility study with ovine caudal discs. Spine 31:2665–2673PubMed

40.

Ghosh P, Bushell GR, Taylor TK, Pearce RH, Grimmer BJ (1980) Distribution of glycosaminoglycans across the normal and the scoliotic disc. Spine 5:310–317PubMed

41.

Ghosh P, Melrose J, Cole TC, Taylor T (1992) A comparison of the high buoyant density proteoglycans isolated from the intervertebral discs of chondrodystrophoid and non-chondrodystrophoid dogs. Matrix 12:148–155PubMed

42.

Ghosh P, Taylor TK, Braund KG (1977) The variation of the glycosaminoglycans of the canine intervertebral disc with ageing. I. Chondrodystrophoid breed. Gerontology 23:87–98PubMed

43.

Ghosh P, Taylor TK, Braund KG (1977) Variation of the glycosaminoglycans of the intervertebral disc with ageing. II. Non-chondrodystrophoid breed. Gerontology 23:99–109PubMed

44.

Ghosh P, Taylor TK, Braund KG, Larsen LH (1976) The collagenous and non-collagenous protein of the canine intervertebral disc and their variation with age, spinal level and breed. Gerontology 22:124–134PubMed

45.

Gillett NA, Gerlach R, Cassidy JJ, Brown SA (1988) Age-related changes in the beagle spine. Acta Orthop Scand 59:503–507PubMedCrossRef

46.

Glant TT, Mikecz K, Arzoumanian A, Poole AR (1987) Proteoglycan-induced arthritis in BALB/c mice. Clinical features and histopathology. Arthritis Rheum 30:201–212PubMed

47.

Hadjipavlou AG, Simmons JW, Yang JP, Bi LX, Ansari GA, Kaphalia BS, Simmons DJ, Nicodemus CL, Necessary JT, Lane R, Esch O (1998) Torsional injury resulting in disc degeneration: I. An in vivo rabbit model. J Spinal Disord 11:312–317PubMed

48.

Hammer RE, Maika SD, Richardson JA, Tang JP, Taurog JD (1990) Spontaneous inflammatory disease in transgenic rats expressing HLA-B27 and human beta 2m: an animal model of HLA-B27-associated human disorders. Cell 63:1099–1112PubMed

49.

Hamrick MW, Pennington C, Byron CD (2003) Bone architecture and disc degeneration in the lumbar spine of mice lacking GDF-8 (myostatin). J Orthop Res 21:1025–1032PubMed

50.

Higuchi M, Abe K, Kaneda K (1983) Changes in the nucleus pulposus of the intervertebral disc in bipedal mice. A light and electron microscopic study. Clin Orthop Relat Res 175:251–257PubMed

51.

Holm S, Holm AK, Ekström L, Karladani A, Hansson T (2004) Experimental disc degeneration due to endplate injury. J Spinal Disord Tech 17:64–71PubMed

52.

Horner HA, Roberts S, Bielby RC, Menage J, Evans H, Urban JPG (2002) Cells from different regions of the intervertebral disc—effect of culture system on matrix expression and cell phenotype. Spine 27:1018–1028PubMed

53.

Horner HA, Urban JPG (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

54.

Hunter CJ, Matyas JR, Duncan NA (2003) The notochordal cell in the nucleus pulposus: a review in the context of tissue engineering. Tissue Eng 9:667–677PubMed

55.

Hunter CJ, Matyas JR, Duncan NA (2004) Cytomorphology of notochordal and chondrocytic cells from the nucleus pulposus: a species comparison. J Anat 205:357–362PubMed

56.

Hutton WC, Murakami H, Li A, Elmer WA, Yoon ST, Minamide A, Akamaru T, Tomita K (2004) The effect of blocking a nutritional pathway to the intervertebral disc in the dog model. J Spinal Disord Tech 17:53–63PubMed

57.

Iatridis JC, MacLean JJ, Roughley PJ, Alini M (2006) Effects of mechanical loading on intervertebral disc metabolism in vivo. J Bone Joint Surg Am 88(Suppl 2):41–46PubMed

58.

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

59.

Johnson WEB, Menage J, Evans H, Gaguilo B, Roberts S, Eisenstein SM (2004) Serum-deprivation is associated with decreased cellularity and a loss of proteoglycan in organ cultures of bovine intervertebral discs. In: Proceedings of the 30th annual meeting, 5-5-1930, Porto, p 223

60.

Kaapa E, Han X, Holm S, Peltonen J, Takala T, Vanharanta H (1995) Collagen synthesis and types I, III, IV, and VI collagens in an animal model of disc degeneration. Spine 20:59–66PubMedCrossRef

61.

Kaapa E, Holm S, Han X, Takala T, Kovanen V, Vanharanta H (1994) Collagens in the injured porcine intervertebral disc. J Orthop Res 12:93–102PubMed

62.

Kaigle AM, Holm SH, Hansson TH (1995) Experimental instability in the lumbar spine. Spine 20:421–430PubMed

63.

Kaigle AM, Holm SH, Hansson TH (1997) 1997 Volvo Award winner in biomechanical studies. Kinematic behavior of the porcine lumbar spine: a chronic lesion model. Spine 22:2796–2806PubMed

64.

Kanemura T, Kawakami N, Deguchi M, Mimatsu K, Iwata H (1997) Natural course of experimental scoliosis in pinealectomized chickens. Spine 22:1563–1567PubMed

65.

Key JA, Ford LT (1948) Experimental intervertebral disc lesions. J Bone Joint Surg Am 30A:621PubMed

66.

Kim KS, Yoon ST, Li J, Park JS, Hutton WC (2005) Disc degeneration in the rabbit: a biochemical and radiological comparison between four disc injury models. Spine 30:33–37PubMed

67.

Kim KW, Ha KY, Park JB, Woo YK, Chung HN, An HS (2005) Expressions of membrane-type I matrix metalloproteinase, Ki-67 protein, and type II collagen by chondrocytes migrating from cartilage endplate into nucleus pulposus in rat intervertebral discs: a cartilage endplate-fracture model using an intervertebral disc organ culture. Spine 30:1373–1378PubMed

68.

Kim KW, Lim TH, Kim JG, Jeong ST, Masuda K, An HS (2003) The origin of chondrocytes in the nucleus pulposus and histologic findings associated with the transition of a notochordal nucleus pulposus to a fibrocartilaginous nucleus pulposus in intact rabbit intervertebral discs. Spine 28:982–990PubMed

69.

Kimura T, Nakata K, Tsumaki N, Miyamoto S, Matsui Y, Ebara S, Ochi T (1996) Progressive degeneration of articular cartilage and intervertebral discs. An experimental study in transgenic mice bearing a type IX collagen mutation. Int Orthop 20:177–181PubMed

70.

Kluba T, Niemeyer T, Gaissmaier C, Grunder T (2005) Human anulus fibrosis and nucleus pulposus cells of the intervertebral disc: effect of degeneration and culture system on cell phenotype. Spine 30:2743–2748PubMed

71.

Krebs J, Ferguson SJ, Goss BG, Aebli N (2006) Degenerative changes of intervertebral discs after vertebroplasty. In: Proceedings of the 33rd annual meeting of the international society for the study of the lumbar spine, Bergen, p 31

72.

Kroeber M, Unglaub F, Guehring T, Nerlich A, Hadi T, Lotz J, Carstens C (2005) Effects of controlled dynamic disc distraction on degenerated intervertebral discs: an in vivo study on the rabbit lumbar spine model. Spine 30:181–187PubMed

73.

Kroeber MW, Unglaub F, Wang HL, 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

74.

Latorre A, Albareda J, Castiella T, Lasierra JM, Seral F (1998) Experimental model of multidirectional disc hernia in rats. Int Orthop 22:44–48PubMed

75.

Lauerman WC, Platenberg RC, Cain JE, Deeney VF (1992) Age-related disk degeneration: preliminary report of a naturally occurring baboon model. J Spinal Disord 5:170–174PubMed

76.

Lee CR, Grad S, MacLean JJ, Iatridis JC, Alini M (2005) Effect of mechanical loading on mRNA levels of common endogenous controls in articular chondrocytes and intervertebral disk. Anal Biochem 341:372–375PubMed

77.

Lee CR, Iatridis JC, Poveda L, Alini M (2006) In vitro organ culture of the bovine intervertebral disc: effects of vertebral endplate and potential for mechanobiology studies. Spine 31:515–522PubMed

78.

Lindblom K (1957) Intervertebral-disc degeneration considered as a pressure atrophy. J Bone Joint Surg Am 39-A:933–945PubMed

79.

Lipson SJ, Muir H (1980) Vertebral osteophyte formation in experimental disc degeneration. Morphologic and proteoglycan changes over time. Arthritis Rheum 23:319–324PubMed

80.

Lipson SJ, Muir H (1981) 1980 Volvo award in basic science. Proteoglycans in experimental intervertebral disc degeneration. Spine 6:194–210PubMed

81.

Lotz JC (2004) Animal models of intervertebral disc degeneration: lessons learned. Spine 29:2742–2750PubMed

82.

Lotz JC, Colliou OK, Chin JR, Duncan NA, Liebenberg E (1998) 1998 Volvo Award winner in biomechanical studies—compression- induced degeneration of the intervertebral disc: an in vivo mouse model and finite-element study. Spine 23:2493–2506PubMed

83.

Lundin O, Ekstrom L, Hellstrom M, Holm S, Sward L (1998) Injuries in the adolescent porcine spine exposed to mechanical compression. Spine 23:2574–2579PubMed

84.

Lundin O, Ekstrom L, Hellstrom M, Holm S, Sward L (2000) Exposure of the porcine spine to mechanical compression: differences in injury pattern between adolescents and adults. Eur Spine J 9:466–471PubMed

85.

Machida M, Dubousset J, Imamura Y, Iwaya T, Yamada T, Kimura J (1993) An experimental study in chickens for the pathogenesis of idiopathic scoliosis. Spine 18:1609–1615PubMed

86.

Machida M, Dubousset J, Imamura Y, Iwaya T, Yamada T, Kimura J (1995) Role of melatonin deficiency in the development of scoliosis in pinealectomised chickens. J Bone Joint Surg Br 77:134–138PubMed

87.

Machida M, Murai I, Miyashita Y, Dubousset J, Yamada T, Kimura J (1999) Pathogenesis of idiopathic scoliosis. Experimental study in rats. Spine 24:1985–1989PubMed

88.

Machida M, Saito M, Dubousset J, Yamada T, Kimura J, Shibasaki K (2005) Pathological mechanism of idiopathic scoliosis: experimental scoliosis in pinealectomized rats. Eur Spine J 14:843–848PubMed

89.

Maeda S, Kokubun S (2000) Changes with age in proteoglycan synthesis in cells cultured in vitro from the inner and outer rabbit annulus fibrosus. Responses to interleukin-1 and interleukin-1 receptor antagonist protein. Spine 25:166–169PubMed

90.

Maldonado BA, Oegema TR Jr (1992) Initial characterization of the metabolism of intervertebral disc cells encapsulated in microspheres. J Orthop Res 10:677–690PubMed

91.

Mason RM, Palfrey AJ (1984) Intervertebral disc degeneration in adult mice with hereditary kyphoscoliosis. J Orthop Res 2:333–338PubMed

92.

Masuda K, Aota Y, Muehleman C, Imai Y, Okuma M, Thonar EJ, Andersson GB, An HS (2005) A novel rabbit model of mild, reproducible disc degeneration by an anulus needle puncture: correlation between the degree of disc injury and radiological and histological appearances of disc degeneration. Spine 30:5–14PubMed

93.

Melrose J, Ghosh P, Taylor TK, Hall A, Osti OL, Vernon-Roberts B, Fraser RD (1992) A longitudinal study of the matrix changes induced in the intervertebral disc by surgical damage to the annulus fibrosus. J Orthop Res 10:665–676PubMed

94.

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 10:55–67PubMed

95.

Melrose J, Ghosh P, Taylor TK, McAuley L (1994) Variation in the composition of the ovine intervertebral disc with spinal level and in its constituent proteoglycans. Vet Comp Orthop Traumatol 7:70–76

96.

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 6:376–384PubMed

97.

Melrose J, Gurr KR, Cole TC, Darvodelsky A, Ghosh P, Taylor TK (1991) The influence of scoliosis and ageing on proteoglycan heterogeneity in the human intervertebral disc. J Orthop Res 9:68–77PubMed

98.

Melrose J, Hall A, Macpherson C, Bellenger CR, Ghosh P (1995) Evaluation of digestive proteinases from the Antarctic krill Euphasia superba as potential chemonucleolytic agents. In vitro and in vivo studies. Arch Orthop Trauma Surg 114:145–152PubMed

99.

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 27:1278–1285PubMed

100.

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 27:1756–1764PubMed

101.

Melrose J, Taylor TK, Ghosh P (1996) Variation in intervertebral disc serine proteinase inhibitory proteins with ageing in a chondrodystrophoid (beagle) and a non-chondrodystrophoid (greyhound) canine breed. Gerontology 42:322–329PubMedCrossRef

102.

Melrose J, Taylor TK, Ghosh P (1997) The serine proteinase inhibitory proteins of the chondrodystrophoid (beagle) and non-chondrodystrophoid (greyhound) canine intervertebral disc. Electrophoresis 18:1059–1063PubMed

103.

Melrose J, Taylor TK, Ghosh P, Holbert C, Macpherson C, Bellenger CR (1996) Intervertebral disc reconstitution after chemonucleolysis with chymopapain is dependent on dosage. Spine 21:9–17PubMed

104.

Mente PL, Aronsson DD, Stokes IAF, Iatridis JC (1999) Mechanical modulation of growth for the correction of vertebral wedge deformities. J Orthop Res 17:518–524PubMed

105.

Mikecz K, Glant TT, Poole AR (1987) Immunity to cartilage proteoglycans in BALB/c mice with progressive polyarthritis and ankylosing spondylitis induced by injection of human cartilage proteoglycan. Arthritis Rheum 30:306–318PubMed

106.

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 24:519–525PubMed

107.

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

108.

Moore RJ, Vernon-Roberts B, Osti OL, Fraser RD (1996) Remodeling of vertebral bone after outer anular injury in sheep. Spine 21:936–940PubMed

109.

Moskowitz RW, Ziv I, Denko CW, Boja B, Jones PK, Adler JH (1990) Spondylosis in sand rats: a model of intervertebral disc degeneration and hyperostosis. J Orthop Res 8:401–411PubMed

110.

Neufeld JH, Machado T, Margolin L (1991) Variables affecting disc size in the lumbar spine of rabbits: anesthesia, paralysis, and disc injury. J Orthop Res 9:104–112PubMed

111.

Norcross JP, Lester GE, Weinhold P, Dahners LE (2003) An in vivo model of degenerative disc disease. J Orthop Res 21:183–188PubMed

112.

O’Kelly C, Wang X, Raso J, Moreau M, Mahood J, Zhao J, Bagnall K (1999) The production of scoliosis after pinealectomy in young chickens, rats, and hamsters. Spine 24:35–43PubMed

113.

Oegema TR, Johnson SL, Aguiar DJ, Ogilvie JW (2000) Fibronectin and its fragments increase with degeneration in the human intervertebral disc. Spine 25:2742–2747PubMed

114.

Olsewski JM, Schendel MJ, Wallace LJ, Ogilvie JW, Gundry CR (1996) Magnetic resonance imaging and biological changes in injured intervertebral discs under normal and increased mechanical demands. Spine 21:1945–1951PubMed

115.

Oshima H, Ishihara H, Urban JP, Tsuji H (1993) The use of coccygeal discs to study intervertebral disc metabolism. J Orthop Res 11:332–338PubMed

116.

Osterman K, Osterman H (1996) Experimental lumbar spondylolisthesis in growing rabbits. Clin Orthop Relat Res 332:274–280PubMed

117.

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 15:762–767PubMed

118.

Park C, Kim YJ, Lee CS, An K, Shin HJ, Lee CH, Kim CH, Shin JW (2005) An in vitro animal study of the biomechanical responses of anulus fibrosus with aging. Spine 30:E259–E265PubMed

119.

Pedrini-Mille A, Weinstein JN, Found EM, Chung CB, Goel VK (1990) Stimulation of dorsal root ganglia and degradation of rabbit annulus fibrosus. Spine 15:1252–1256PubMed

120.

Peng BG, Hou SX, Shi Q, Jia LS (2001) The relationship between cartilage end-plate calcification and disc degeneration: an experimental study. Chin Med J 114:308–312PubMed

121.

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 207:299–312PubMed

122.

Phillips FM, Reuben J, Wetzel FT (2002) Intervertebral disc degeneration adjacent to a lumbar fusion—an experimental rabbit model. J Bone Joint Surg Br 84B:289–294

123.

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

124.

Puustjarvi K, Lammi M, Kiviranta I, Helminen HJ, Tammi M (1993) Proteoglycan synthesis in canine intervertebral discs after long-distance running training. J Orthop Res 11:738–746PubMed

125.

Rannou F, Poiraudeau S, Foltz V, Boiteux M, Corvol M, Revel M (2000) Monolayer anulus fibrosus cell cultures in a mechanically active environment: local culture condition adaptations and cell phenotype study. J Lab Clin Med 136:412–421PubMed

126.

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

127.

Saamanen AM, Puustjarvi K, Ilves K, Lammi M, Kiviranta I, Jurvelin J, Helminen HJ, Tammi M (1993) Effect of running exercise on proteoglycans and collagen content in the intervertebral disc of young dogs. Int J Sports Med 14:48–51PubMed

128.

Sahlman J, Inkinen R, Hirvonen T, Lammi MJ, Lammi PE, Nieminen J, Lapvetelainen T, Prockop DJ, Arita M, Li SW, Hyttinen MM, Helminen HJ, Puustjarvi K (2001) Premature vertebral endplate ossification and mild disc degeneration in mice after inactivation of one allele belonging to the Col2a1 gene for Type II collagen. Spine 26:2558–2565PubMed

129.

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

130.

Sarver JJ, Elliott DM (2005) Mechanical differences between lumbar and tail discs in the mouse. J Orthop Res 23:150–155PubMed

131.

Shi S, Ciurli C, Cartman A, Pidoux I, Poole AR, Zhang Y (2003) Experimental immunity to the G1 domain of the proteoglycan versican induces spondylitis and sacroiliitis, of a kind seen in human spondylarthropathies. Arthritis Rheum 48:2903–2915PubMed

132.

Smith JW, Walmsley R (1951) Experimental incision of the intervertebral disc. J Bone Joint Surg Br 33-B:612–625PubMed

133.

Sobajima S, Kompel JF, Kim JS, Wallach CJ, Robertson DD, Vogt MT, Kang JD, Gilbertson LG (2005) A slowly progressive and reproducible animal model of intervertebral disc degeneration characterized by MRI, X-ray, and histology. Spine 30:15–24PubMed

134.

Stevens JW, Kurriger GL, Carter AS, Maynard JA (2000) CD44 expression in the developing and growing rat intervertebral disc. Dev Dyn 219:381–390PubMed

135.

Stokes IA, Aronsson DD, Spence H, Iatridis JC (1998) Mechanical modulation of intervertebral disc thickness in growing rat tails. J Spinal Disord 11:261–265PubMed

136.

Stokes IA, Counts DF, Frymoyer JW (1989) Experimental instability in the rabbit lumbar spine. Spine 14:68–72PubMed

137.

Stokes IA, Iatridis JC (2004) Mechanical conditions that accelerate intervertebral disc degeneration: overload versus immobilization. Spine 29:2724–2732PubMed

138.

Suguro T, Oegema TR Jr, Bradford DS (1986) Ultrastructural study of the short-term effects of chymopapain on the intervertebral disc. J Orthop Res 4:281–287PubMed

139.

Sweet HO, Green MC (1981) Progressive ankylosis, a new skeletal mutation in the mouse. J Hered 72:87–93PubMed

140.

Takaishi H, Nemoto O, Shiota M, Kikuchi T, Yamada H, Yamagishi M, Yabe Y (1997) Type-II collagen gene expression is transiently upregulated in experimentally induced degeneration of rabbit intervertebral disc. J Orthop Res 15:528–538PubMed

141.

Taurog JD, Maika SD, Satumtira N, Dorris ML, McLean IL, Yanagisawa H, Sayad A, Stagg AJ, Fox GM, Le O’Brien A, Rehman M, Zhou M, Weiner AL, Splawski JB, Richardson JA, Hammer RE (1999) Inflammatory disease in HLA-B27 transgenic rats. Immunol Rev 169:209–223PubMed

142.

Taylor TK, Ghosh P, Braund KG, Sutherland JM, Sherwood AA (1976) The effect of spinal fusion on intervertebral disc composition: an experimental study. J Surg Res 21:91–104PubMed

143.

Taylor TK, Melrose J, Burkhardt D, Ghosh P, Claes LE, Kettler A, Wilke HJ (2000) Spinal biomechanics and aging are major determinants of the proteoglycan metabolism of intervertebral disc cells. Spine 25:3014–3020PubMed

144.

Thometz JG, Liu XC, Lyon R (2000) Three-dimensional rotations of the thoracic spine after distraction with and without rib resection: a kinematic evaluation of the apical vertebra in rabbits with induced scoliosis. J Spinal Disord 13:108–112PubMed

145.

Thompson RE, Pearcy MJ, Barker TM (2004) The mechanical effects of intervertebral disc lesions. Clin Biomech 19:448–455

146.

Turgut M, Basaloglu HK, Yenisey C, Ozsunar Y (2006) Surgical pinealectomy accelerates intervertebral disc degeneration process in chicken. Eur Spine J 15:605–612PubMed

147.

Urayama S (1986) Histological and ultrastructural study of degeneration of the lumbar intervertebral disc in the rabbit following nucleotomy, with special reference to the topographical distribution pattern of the degeneration. Nippon Seikeigeka Gakkai Zasshi 60:649–662PubMed

148.

van der Werf MJ, Lezuo P, Maissen O, Ito K (2006) Decreased diffusion as a result of perfusion block in the ovine lumbar spine: a future model for disc degeneration. In: Proceedings of the 52nd annual meeting of the orthopaedic research society, Chicago, IL, p 31

149.

Walsh AJL, Lotz JC (2004) Biological response of the intervertebral disc to dynamic loading. J Biomech 37:329–337PubMed

150.

Wang JY, Baer AE, Kraus VB, Setton LA (2001) Intervertebral disc cells exhibit differences in gene expression in alginate and monolayer culture. Spine 26:1747–1751PubMed

151.

Wang X, Jiang H, Raso J, Moreau M, Mahood J, Zhao J, Bagnall K (1997) Characterization of the scoliosis that develops after pinealectomy in the chicken and comparison with adolescent idiopathic scoliosis in humans. Spine 22:2626–2635PubMed

152.

Watanabe H, Nakata K, Kimata K, Nakanishi I, Yamada Y (1997) Dwarfism and age-associated spinal degeneration of heterozygote cmd mice defective in aggrecan. Proc Natl Acad Sci USA 94:6943–6947PubMed

153.

Watanabe H, Yamada Y (2002) Chondrodysplasia of gene knockout mice for aggrecan and link protein. Glycoconj J 19:269–273PubMed

154.

Weinreich S, Hoebe B, Ivanyi P (1995) Maternal age influences risk for HLA-B27 associated ankylosing enthesopathy in transgenic mice. Ann Rheum Dis 54:754–756PubMedCrossRef

155.

Wilke HJ, Kettler A, Claes LE (1997) Are sheep spines a valid biomechanical model for human spines? Spine 22:2365–2374PubMed

156.

Wilke HJ, Kettler A, Gosh P, Claes L (1999) Is the lumbar sheep spine an adequate model for the human lumbar spine?—a comparison of biomechanical properties, macroscopic and microscopic anatomy and bone mineral density. In: Proceedings of the 26th annual meeting, Hawaii, p 124

157.

Wilke HJ, Kettler A, Wenger KH, Claes LE (1997) Anatomy of the sheep spine and its comparison to the human spine. Anat Rec 247:542–555PubMed

158.

Wilke HJ, Krischak ST, Wenger KH, Claes LE (1997) Load-displacement properties of the thoracolumbar calf spine: experimental results and comparison to known human data. Eur Spine J 6:129–137PubMed

159.

Wilke HJ, Rohlmann A, Neller S, Graichen F, Claes L, Bergmann G (2003) ISSLS prize winner: a novel approach to determine trunk muscle forces during flexion and extension: a comparison of data from an in vitro experiment and in vivo measurements. Spine 28:2585–2593PubMed

160.

White AA, Panjabi MM (1990) Clinical Biomechanics of the Spine. 2nd edn. JB Lippincott Company

161.

Yamada K, Tanabe S, Eueno H, Oinuma A, Ytakahashi T, Mityauchi S, Shigeno S, Hirose T, Miyahara K, Sato M (2001) Investigation of the short term effect of chemonucleolysis with chondroitinase ABC. J Vet Med Sci 63: 521–525PubMed

Title: Are animal models useful for studying human disc disorders/degeneration?
Authors: Mauro Alini
Stephen M. Eisenstein
Keita Ito
Christopher Little
A. Annette Kettler
Koichi Masuda
James Melrose
Jim Ralphs
Ian Stokes
Hans Joachim Wilke
Publication date: 01-01-2008
Publisher: Springer-Verlag
Published in: European Spine Journal / Issue 1/2008
Print ISSN: 0940-6719
Electronic ISSN: 1432-0932
DOI: https://doi.org/10.1007/s00586-007-0414-y

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Are animal models useful for studying human disc disorders/degeneration?

Abstract

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Abstract

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