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Clinical Orthopaedics and Related Research®

Erschienen in:

01.06.2015 | Symposium: Current Approaches to the Management of Lumbar Disc Herniation

Molecular Basis of Intervertebral Disc Degeneration and Herniations: What Are the Important Translational Questions?

verfasst von: Tiffany Kadow, MD, Gwendolyn Sowa, MD, PhD, Nam Vo, PhD, James D. Kang, MD

Erschienen in: Clinical Orthopaedics and Related Research® | Ausgabe 6/2015

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Abstract

Background

Intervertebral disc degeneration is a common condition with few inexpensive and effective modes of treatment, but current investigations seek to clarify the underlying process and offer new treatment options. It will be important for physicians to understand the molecular basis for the pathology and how it translates to developing clinical treatments for disc degeneration. In this review, we sought to summarize for clinicians what is known about the molecular processes that causes disc degeneration.

Results

A healthy disc requires maintenance of a homeostatic environment, and when disrupted, a catabolic cascade of events occurs on a molecular level resulting in upregulation of proinflammatory cytokines, increased degradative enzymes, and a loss of matrix proteins. This promotes degenerative changes and occasional neurovascular ingrowth potentially contributing to the development of pain. Research demonstrates the molecular changes underlying the harmful effects of aging, smoking, and obesity seen clinically while demonstrating the variable influence of exercise. Finally, oral medications, supplements, biologic treatments, gene therapy, and stem cells hold great promise but require cautious application until their safety profiles are better outlined.

Conclusions

Intervertebral disc degeneration occurs where there is a loss of homeostatic balance with a predominantly catabolic metabolic profile. A basic understanding of the molecular changes occurring in the degenerating disc is important for practicing clinicians because it may help them to inform patients to alter lifestyle choices, identify beneficial or harmful supplements, or offer new biologic, genetic, or stem cell therapies.

Abe Y, Akeda K, An HS, Aoki Y, Pichika R, Muehleman C, Kimura T, Masuda K. Proinflammatory cytokines stimulate the expression of nerve growth factor by human intervertebral disc cells. Spine (Phila Pa 1976). 2007;32:635–642.

Akmal M, Kesani A, Anand B, Singh A, Wiseman M, Goodship A. Effect of nicotine on spinal disc cells: a cellular mechanism for disc degeneration. Spine (Phila Pa 1976). 2004;29:568–575.

An HS, Takegami K, Kamada H, Nguyen CM, Thonar EJ, Singh K, Andersson GB, Masuda K. Intradiscal administration of osteogenic protein-1 increases intervertebral disc height and proteoglycan content in the nucleus pulposus in normal adolescent rabbits. Spine (Phila Pa 1976). 2005;30:25–31.

Andersson G. Epidemiological features of chronic low back pain. Lancet. 1999;354:581–585.PubMed

Aoki Y, Takahashi Y, Ohtori S, Moriya H, Takahashi K. Distribution and immunocytochemical characterization of dorsal root ganglion neurons innervating the lumbar intervertebral disc in rats: a review. Life Sci. 2004;74:2627–2642.PubMed

Bank RA, Bayliss MT, Lafeber FP, Maroudas A, Tekoppele JM. Ageing and zonal variation in post-translational modification of collagen in normal human articular cartilage. The age-related increase in non-enzymatic glycation affects biomechanical properties of cartilage. Biochem J. 1998;330:345–351.PubMedCentralPubMed

Barnes P, Powell-Griner E, McFann K, Nahin RL. Complementary and alternative medicine use among adults: United States, 2002. Adv Data. 2004;343:1–19.PubMed

Battie MC, Videman T, Gill K, Moneta GB, Nyman R, Kaprio J, Koskenvuo M. 1991 Volvo Award in Clinical Sciences. Smoking and lumbar intervertebral disc degeneration: an MRI study of identical twins. Spine (Phila Pa 1976). 1991;16:1015–1021.

Boos N, Weissbach S, Rohrbach H. Classification of age related changes in lumber intervertebral discs. Spine. 2002;27:2631–2644.PubMed

10.

Buckwalter JA, Smith KC, Kazarien LE, Rosenberg LC, Ungar R. Articular cartilage and intervertebral disc proteoglycans differ in structure: an electron microscopic study. J Orthop Res. 1989;7:146–151.PubMed

11.

Chen D, Zhao M, Harris SE, Mi Z. Signal transduction and biologic functions of bone morphogenetic proteins. Front Biosci. 2004;9:349–358.PubMed

12.

Chen HT, Lee MJ, Chen CH, Chuang SC, Chang LF, Ho ML, Hung SH, Fu YC, Wang YH, Wang HI, Wang GJ, Kang L, Chang JK. Proliferation and differentiation potential of human adipose-derived mesenchymal stem cells isolated from elderly patients with osteoporotic fractures. J Cell Mol Med. 2012;16:582–593.PubMedCentralPubMed

13.

Cleland LG. Clinical and biochemical effects of dietary fish oil supplements in rheumatoid arthritis. J Rheumatol. 1988;15:1471–1475.PubMed

14.

Considine RV, Sinha MK, Heiman ML, Kriauciunas A, Stephens TW, Nyce MR, Ohannesian JP, Marco CC, McKee LJ, Bauer TL, et al. Serum immunoreactive-leptin concentrations in normal-weight and obese humans. N Engl J Med. 1996;334:292–295.PubMed

15.

Coppes MH, Marani E, Thomeer RT, Groen GJ. Innervation of ‘painful’ lumbar discs. Spine. 1997;22:2342–2349.PubMed

16.

DeGroot J, Verzijl N, Bank RA, Lafeber FP, Bijisma JW, TeKoppele JM. Age-related decrease in proteoglycan synthesis of human articular chondrocytes: the role of nonenzymatic glycation. Arthritis Rheum. 1999;42:1003–1009.PubMed

17.

Diamond J, Coughlin M, Macintyre L, Holmes M, Visheau B. Evidence that endogenous beta nerve growth factor is responsible for the collateral sprouting, but not the regeneration, of nociceptive axons in adult rats. Proc Natl Acad Sci USA. 1987;84:6596–6600.PubMedCentralPubMed

18.

Di Virgilio F. New pathways for reactive oxygen species generation in inflammation and potential novel pharmacological targets. Curr Pharm Des. 2004;10:1647–1652.PubMed

19.

Drazin D, Rosner J, Avalos P, Acosta F. Stem cell therapy for degenerative disc disease. Adv Orthop. 2012;2012:961052.PubMedCentralPubMed

20.

Fardon DF, Milette PC. Nomenclature and classification of lumbar disc pathology: Recommendations of the combined task forces of the North American Spine Society, American Society of Spine Radiology, and American Society of Neuroradiology. Spine (Phila Pa 1976). 2001;26:E93–E113.

21.

Finkel T, Holbrook JN. Oxidants, oxidative stress and the biology of ageing. Nature. 2000;408:239–247.PubMed

22.

Frank A. Low back pain. BMJ. 1993;306:901–908.PubMedCentralPubMed

23.

Freeman BJ, Fraser RD, Cain CM, Hall DJ, Chapple DC. A randomized, doubleblind, controlled trial: intradiscal electrothermal therapy versus placebo for the treatment of chronic discogenic low back pain. Spine (Phila Pa 1976) 2005;30:2369–2377.

24.

Freemont AJ, Peacock TE, Goupille P, Hoyland JA, O’Brien J, Jayson MI. Nerve ingrowth into diseased intervertebral disc in chronic back pain. Lancet. 1997;350:178–181.PubMed

25.

Freemont AJ, Watkins A, Le Maitre C, Baird P, Jeziorska M, Knight MT, Ross ER, O’Brien JP, Hoyland J. Nerve growth factor expression and innervation of the painful intervertebral disc. J Pathol. 2002;197:286–292.PubMed

26.

Gordon SJ, Yang KH, Mayer PJ, Mace AH, Kish VL, Radin EL. Mechanism of disc rupture: a preliminary report. Spine (Phila Pa 1976). 1991;16:450–456.

27.

Gruber HE, Ingram JA, Hoelscher GL, Hanley EN Jr. Leptin expression by annulus cells in the human intervertebral disc. Spine J. 2007;7:437–443.PubMed

28.

Handa T, Ishihara H, Ohshima H, Osada R, Tsuji H, Obata K. Effects of hydrostatic pressure on matrix synthesis and matrix metalloproteinase production in the human lumbar intervertebral disc. Spine (Phila Pa 1976). 1997;22:1085–1091.

29.

Haschtmann D, Ferguson SJ, Stoyanov JV. BMP-2 and TFG-β3 do not prevent spontaneous degeneration in rabbit disc explants but induce ossification of the annulus fibrosus. Eur Spine J. 2012;21:1724–1733.PubMedCentralPubMed

30.

Hiu W, Litherland GJ, Elias MS, Kitson GI, Cawston TE, Rowan AD, Young DA. Leptin produced by joint white adipose tissue induces cartilage degradation and upregulation and activation of matrix metalloproteinases. Ann Rheum Dis. 2012;71:455–462.

31.

Imai Y, Okuma M, An HS, Nakagawa K, Yamada M, Muehleman C, Thonar E, Masuda K. Restoration of disc height loss by recombinant human osteogenic protein-1 injection into intervertebral discs undergoing degeneration induced by an intradiscal injection of chondroitinase ABC. Spine (Phila Pa 1976). 2007;32:1197–1205.

32.

Kaigle AM, Holm SH, Hansson TH. Kinematic behavior of the porcine lumbar spine: a chronic lesion model. Spine. 1997;22:2796–2806.PubMed

33.

Jacobs L, Vo N, Coehlo JP, Dong Q, Bechara B, Woods B, Hempen E, Hartman R, Preuss H, Balk J, Kang J, Sowa G. Glucosamine supplementation demonstrates a negative effect on intervertebral disc matrix in an animal model of disc degeneration. Spine. 2013 Jan 15 [Epub ahead of print].

34.

Kawakami M, Matsumoto T, Hashizume H, Kuribayashi K, Chubinskaya S, Yoshida M. 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 (Phila Pa 1976). 2005;30:1933–1939.

35.

Kim H, Lee JU, Moon SH, Kim HC, Kwon UH, Seol NH, Kim HJ, Park JO, Chun HJ, Kwon IK, Lee HM. Zonal responsiveness of the human intervertebral disc to bone morphogenetic protein-2. Spine. 2009;34:1834–1838.PubMed

36.

Kim HJ, Studer RK, Sowa GA, Vo NV, Kang JD. Activated macrophage-like THP-1 cells modulate annulus fibrosus cell production of inflammatory mediators in response to cytokines. Spine (Phila Pa 1976). 2008;33:2253–2259.

37.

Kim JS, Ellman MB, An HS, van Wijinen AJ, Borgia JA, Im JH. Insulin-like growth factor 1 synergizes with bone morphogenetic protein 7-mediated anabolism in bovine intervertebral disc cells. Arthritis Rheum. 2010;62:3706–3715.PubMedCentralPubMed

38.

Kim KW, Ha KY, Lee JS, Rhyu KW, An HS, Woo YK. The apoptotic effect of oxidative stress and antiapoptotic effect of caspase inhibitors on rat notochordal cells. Spine. 2007;32:2443–2448.PubMed

39.

Koch A, Zacharowski K, Boehm O, Stevens M, Lipfert P, von Giesen HJ, Wolf A, Freynhagen R. Nitric oxide and pro-inflammatory cytokines correlate with pain intensity in chronic pain patients. Inflamm Res. 2007;56:32–37.PubMed

40.

Kuga N, Kawabuchi M. Histology of intervertebral disc protrusion: an experimental study using an aged rat model. Spine (Phila Pa 1976). 2001;26:E379–E384.

41.

Leckie SK, Bechara BP, Hartman RA, Sowa GA, Woods BI, Coelho JP, Witt WT, Dong QD, Bowman BW, Bell KM, Vo NV, Wang B, Kang JD. Injection of AAV2-BMP2 and AAV2-TIMP1 into the nucleus pulposus slows the course of intervertebral disc degeneration in an in vivo rabbit model. Spine J. 2012;12:7–20.PubMed

42.

Lee CR, Sakai D, Nakai T, Toyama K, Mochida J, Alini M, Grad S. A phenotypic comparison of intervertebral disc and articular cartilage cells in the rat. Eur Spine J. 2007;16:2174–2185.PubMedCentralPubMed

43.

Lee JM. Interleukin-1B induces angiogenesis and innervations of human intervertebral disc degeneration. J Orthop Res. 2011;29:265–269.PubMed

44.

Le Maitre CL, Baird P, Freemont AJ, Hoyland JA. An in vitro study investigating the survival and phenotype of mesenchymal stem cells following injection into nucleus pulposus tissue. Arthritis Res Ther. 2009;11:R20.PubMedCentralPubMed

45.

Le Maitre CL, Hoyland JA, Freemont AJ. Interleukin-1 receptor antagonist delivered directly and by gene therapy inhibits matrix degradation in the intact degenerate human intervertebral disc: an in situ zymographic and gene therapy study. Arthritis Res Ther. 2007;9:R83.PubMedCentralPubMed

46.

Lewin GR, Ritter AM, Mendell LM. Nerve growth factor-induced hyperalgesia in the neonatal and adult rat. J Neurosci. 1993;13:2136–2148.PubMed

47.

Li J, Yoon ST, Hutton WC. Effect of bone morphogenetic protein-2 (BMP-2) on matrix production, other BMPs, and BMP receptors in rat intervertebral disc cells. J Spinal Disord Tech. 2004;17:423–428.PubMed

48.

Li S, Duance VC, Blain EJ. Zonal variations in cytoskeletal element organization, mRNA and protein expression in the intervertebral disc. J Anat. 2008;213:725–732.PubMedCentralPubMed

49.

Li Z, Shen J, Wu WK, Yu X, Liang J, Qiu G, Liu J. Leptin induces cycle D1 expression and proliferation of human nucleus pulposus cells via JAK/STAT, PI3K/Akt and MER/ERK pathways. PLoS One. 2012;7:e53176.PubMedCentralPubMed

50.

Liuke M, Solovieva S, Lamminen A, Luoma K, Leino-Arjas P, Luukkonen R, Riihimaki H. Disc degeneration of the lumbar spine in relation to overweight. Int J Obes (Lond). 2005;29:903–908.

51.

Longo UG, Papapietro N, Petrillo S, Franceschetti E, Maffulli N, Denaro V. Mesenchymal stem cell for prevention and management of intervertebral disc degeneration. Stem Cells Int. 2012;2012:921053.PubMedCentralPubMed

52.

Lotz JC, Hsieh AH, Walsh AL, Palmer EI, Chin JR. Mechanobiology of the intervertebral disc. Biochem Soc Trans. 2002;30:853–858.PubMed

53.

Luo X, Pietrobon R, Sun S, Liu G, Hey L. Estimates and patterns of direct health care expenditures among individuals with back pain in the United States. Spine. 2004;29:79–86.PubMed

54.

Luoma K, Riihimaki H, Raininko R, Luukkonen R, Lamminen A, Viikari-Juntura E. Lumbar disc degeneration in relation to occupation. Scand J Work Environ Health. 1998;24:358–366.PubMed

55.

Madigan L, Vaccaro A, Spector L, Milam R. Management of symptomatic lumbar degenerative disk disease. J Am Acad Orthop Surg. 2009;17:102–111.PubMed

56.

Malinsky J. The ontogenetic development of nerve terminations in the intervertebral discs of man: histology of intervertebral discs, 11th communication. Acta Anat (Basel). 1959;38:96–113.PubMed

57.

Maroon JC, Bost JW. Omega-3 fatty acids (fish oil) as an anti-inflammatory: an alternative to nonsteroidal anti-inflammatory drugs for discogenic pain. Surg Neurol. 2006;65:326–331.PubMed

58.

Masuda K, Imai Y, Okuma M, Muehleman C, Nakagawa K, Akeda K, Thonar E, Andersson G, An HS. Osteogenic protein-1 injection into a degenerated disc induces the restoration of disc height and structural changes in the rabbit annular puncture model. Spine (Phila Pa 1976). 2006;31:742–754.

59.

Mavrogonatou E, Kletsas D. The effect of glucosamine sulfate on the proliferative potential and glycosaminoglycan synthesis of nucleus pulposus intervertebral disc cells. Spine. 2013;38:308–314.PubMed

60.

Miyamoto K, An H, Pichika R, Thonar E, Masuda K. Tumor necrosis factor α inhibits proteoglycan metabolism and stimulates matrix metalloproteinase and aggrecanese production by human intervertebral disc cells. Spine J. 2004;4(Suppl):S66.

61.

Miyamoto T, Muneta T, Tabuchi T, Matsumoto K, Saito H, Tsuji K, Sekiya I. Intradiscal transplantation of synovial mesenchymal stem cells prevents intervertebral disc degeneration through suppression of matrix metalloproteinase-related genes in nucleus pulposus cells in rabbits. Arthritis Res Ther. 2010;12:R206.PubMedCentralPubMed

62.

Montini E, Cesana D, Schmidt M, Sanvito F, Ponzoni M, Bartholomae C, Sergi Sergi L, Benedicenti F, Ambrosi A, Di Serio C, Doglioni C, von Kalle C, Naldini L. Hematopoietic stem cell gene transfer in a tumor-prone mouse model uncovers low genotoxicity of lentiviral vector integration. Nat Biotechnol. 2006;24:687–696.PubMed

63.

Nemoto Y, Matsuzaki H, Tokuhasi Y, Okawa A, Uematu Y, Nishimura T, Oda H. Histological changes in intervertebral discs after smoking and cessation: experimental study using a rat passive smoking model. J Orthop Sci. 2006;11:191–197.PubMed

64.

Nerlich AG, Bachmeier BE, Schleicher E, Rohrbach H, Paesold G, Boos N. Immunomorphological analysis of RAGE receptor expression and NF-kappaB activation in tissue samples from normal and degenerated intervertebral discs of various ages. Ann N Y Acad Sci. 2007;1096:239–248.PubMed

65.

Nishida K, Kang JD, Suh JK, Robbins PD, Evans CH, Gilbertson LG. Adenovirus-mediated gene transfer to nucleus pulposus cells: implications for the treatment of intervertebral disc degeneration. Spine (Phila Pa 1976). 1998;23:2437–2442.

66.

Ogawa T, Matsuzaki H, Uei H, Nakajima S, Tokuhashi Y, Esumi M. Alteration of gene expression in intervertebral disc degeneration of passive cigarette-smoking rats: separate quantitation in separated nucleus pulposus and annulus fibrosus. Pathobiology. 2005;72:146–151.PubMed

67.

Osti O, Vernon-Roberts B, Fraser R. Anulus tears and intervertebral disc degeneration—an experimental study using an animal model. Spine. 1990;15:299–306.

68.

Ou YS, Tan C, An H, Jiang DM, Quan ZX, Tang K, Luo XJ. The effects of NSAIDs on types I, II, and III collagen metabolism in a rat osteoarthritis model. Rheumatol Int. 2012;32:2401–2405.PubMed

69.

Penaud-Budloo M, Le Guiner C, Nowrouzi A, Toromanoff A, Chérel Y, Chenuaud P, Schmidt M, von Kalle C, Rolling F, Moullier P, Snyder RO. Adeno-associated virus vector genomes persist as episomal chromatin in primate muscle. J Virol. 2008;82:7875–7885.PubMedCentralPubMed

70.

Peng B, Hao J, Wu W, Jiang D, Fu X, Yang Y. Possible pathogenesis of painful intervertebral disc degeneration. Spine (Phila Pa 1976). 2006;31:560–566.

71.

Phillips KL, Jordan-Mahy N, Nicklin MJ, Le Maitre CL. Interleukin-1 receptor antagonist deficient mice provide insights into pathogenesis of human intervertebral disc degeneration. Ann Rheum Dis. 2013;72:1860–1867.PubMed

72.

Rajasekaran S, Bajaj N, Tabaki V, Kanna R, Prasad Shetty A. The Anatomy of failure in lumbar disc herniation: an in vivo, multimodal, prospective study of 181 subjects. Spine. 2013;38:1491–1500.PubMed

73.

Richardson SM, Walker RV, Parker S, Rhodes NP, Hunt JA, Freemont AJ, Hoyland JA. Intervertebral disc cell-mediated mesenchymal stem cell differentiation. Stem Cells. 2006;24:707–716.PubMed

74.

Risbud MV, Guttapalli A, Tsai TT, Lee JY, Danielson KG, Vaccaro AR, Albert TJ, Gazit Z, Gazit D, Shapiro IM. Evidence for skeletal progenitor cells in the degenerate human intervertebral disc. Spine. 2007;32:2537–2544.PubMed

75.

Risbud MV, Shapiro IM. Notochordal cells in the adult intervertebral disc: new perspective on an old question. Crit Rev Eukaryot Gene Expr. 2011;21:29–41.PubMedCentralPubMed

76.

Roelofs P, Deyo R, Koes B, Scholten R, van Tulder M. Nonsteroidal anti-inflammatory drugs for low back pain: an updated Cochrane review. Spine (Phila Pa 1976). 2008;33:1766–1774.

77.

Sadowski T, Steinmeyer J. Effects of non-steroidal antiinflammatory drugs and dexamethasone on the activity and expression of matrix metalloproteinase-1, matrix metalloproteinase-3, and tissue inhibitor of metalloproteinases-1 by bovine articular chondrocytes. Osteoarthritis Cartilage. 2001;9:407–415.PubMed

78.

Sakai D, Mochida J, Iwashina T, Hiyama A, Omi H, Imai M, Nakai T, Ando K, Hotta T. Regenerative effects of transplanting mesenchymal stem cells embedded in atelocollagen to the degenerated intervertebral disc. Biomaterials. 2006;27:335–345.PubMed

79.

Sakai D, Mochida J, Iwashina T, Watanabe T, Nakai T, Ando K, Hotta T. Differentiation of mesenchymal stem cells transplanted to a rabbit degenerative disc model: potential and limitations for stem cell therapy in disc regeneration. Spine (Phila Pa 1976). 2005;30:2379–2387.

80.

Sakai D, Mochida J, Yamamoto Y, Nomura T, Okuma M, Nishimura K, Nakai T, Ando K, Hotta T. Transplantation of mesenchymal stem cells embedded in atelocollagen gel to the intervertebral disc: a potential therapeutic model for disc degeneration. Biomaterials. 2003;24:3531–3541.PubMed

81.

Samartzis D, Karppinen J, Chan D, Luk KD, Cheung KM. The association of lumbar intervertebral disc degeneration on magnetic resonance imaging with body mass index in overweight and obese adults: a population-based study. Arthritis Rheum. 2012;64:1488–1496.PubMed

82.

Sinclair SM, Shamji MF, Chen J, Jing L, Richardson WJ, Brown CR, Fitch RD, Setton LA. Attenuation of inflammatory events in human intervertebral disc cells with a tumor necrosis factor antagonist. Spine. 2011;36:1190–1196.PubMedCentralPubMed

83.

Sivan SS, Tsitron E, Wachtel E, Roughley P, Sakkee N, van der Ham F, Degroot J, Maroudas A. Age-related accumulation of pentosidine in aggrecan and collagen from normal and degenerate human intervertebral discs. Biochem J. 2006;399:29–35.PubMedCentralPubMed

84.

Smith RL, Kajiyama G, Lane NE. Nonsteroidal anti-inflammatory drugs: effects on normal and interleukin 1 treated human articular chondrocyte metabolism in vitro. J Rheumatol. 1995;22:1130–1137.PubMed

85.

Sowa G, Coelho P, Vo N, Bedison R, Chiao A, Davies C, Studer R, Kang J. Determination of annulus fibrosus cell response to tensile strain as a function of duration, magnitude, and frequency. J Orthop Res. 2011;29:1275–1283.PubMedCentralPubMed

86.

Sowa G, Westrick E, Pacek C, Coelho P, Patel D, Vadala G, Georgescu H, Vo N, Studer R, Kang J. In vitro and in vivo testing of a novel regulatory system for gene therapy for intervertebral disc degeneration. Spine (Phila Pa 1976). 2011;36:E623–E628.

87.

Srinivas GR, Chichester CO, Barrach HJ, Matoney AL. Effects of certain antiarthritic agents on the synthesis of type II collagen and glycosaminoglycans in rat chondrosarcoma cultures. Agents Actions. 1994;41:193–199.PubMed

88.

Steck E, Bertram H, Abel R, Chen B, Winter A, Richter W. Induction of intervertebral disc-like cells from adult mesenchymal stem cells. Stem Cells. 2005;23:403–411.PubMed

89.

Takahashi T, Uemura Y, Taguchi H, Ogawa Y, Yoshida S, Toda M, Kobayashi T, Seguchi H, Tani T. Cross talk between COX-2 inhibitor and hyaluronic acid in osteoarthritic chondrocytes. Int J Mol Med. 2004;14:139–144.PubMed

90.

Takatalo J, Karppinen J, Taimela S, Niinimaki J, Laitinen J, Sequeiros RB, Samartzis D, Korpelainen R, Nayha S, Remes J, Tervonen O. Association of abdominal obesity with lumbar disc degeneration—a magnetic resonance imaging study. PLoS One. 2013;8:e56244.PubMedCentralPubMed

91.

Taylor VM, Deyo RA, Cherkin DC, Kreuter W. Low-back pain hospitalization: recent United States trends and regional variations. Spine. 1994;19:1207–1213.PubMed

92.

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

93.

Thompson RE, Pearcy MJ, Downing JK, Manthey BA, Parkinson IH, Fazzalari NL. Disc lesions and the mechanics of the intervertebral joint complex. Spine. 2000;20:3026–3035.

94.

Urban JP, Maroudas A. Swelling of the intervertebral disc in vitro. Connect Tissue Res. 1981;9:1–10.PubMed

95.

Vadalà G, Sowa G, Hubert M, Gilbertson LG, Denaro V, Kang JD. Mesenchymal stem cells injection in degenerated intervertebral disc: cell leakage may induce osteophyte formation. J Tissue Eng Regen Med. 2012;6:348–355.PubMed

96.

Vadalà G, Sowa GA, Smith L, Hubert MG, Levicoff EA, Denaro V, Gilbertson LG, Kang JD. Regulation of transgene expression using an inducible system for improved safety of intervertebral disc gene therapy. Spine (Phila Pa 1976). 2007;32:1381–1387.

97.

Veres SP, Robertson PA, Broom ND. ISSLS Prize Winner. How loading rate influences disc failure mechanics: a microstructural assessment of internal disruption. Spine (Phila Pa 1976). 2010;35:1897–1908.

98.

Videman T, Nurminen M, Troup JD. 1990 Volvo Award in clinical sciences. Lumbar spinal pathology in cadaveric material in relation to history of back pain, occupation, and physical loading. Spine. 1990;15:28–40.

99.

Vo N, Wang D, Sowa G, Witt W, Ngo K, Coelho P, Bedison R, Byer B, Studer R, Lee J, Di YP, Kang J. Differential effects of nicotine and tobacco smoke condensate on human annulus fibrosus cell metabolism. J Orthop Res. 2011;29:1585–1591.PubMed

100.

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

101.

Walsh AJ, O’Neill CW, Lotz JC. Glucosamine HCl alters production of inflammatory mediators by rat intervertebral disc cells in vitro. Spine J. 2007;7:601–608.PubMed

102.

Wang D, Nasto LA, Roughley P, Leme AS, Houghton AM, Usas A, Sowa G, Lee J, Niederhofer L, Shapiro S, Kang JD, Vo N. Spine degeneration in a murine model of chronic human tobacco smokers. Osteoarthritis Cartilage. 2012:20:896–905.PubMedCentralPubMed

103.

Wang J, Markova D, Anderson DG, Zheng Z, Shapiro IM, Risbud MV. TNF-α and IL-1β promote a disintegrin-like and metalloprotease with thrombospondin type I motif-5-mediated aggrecan degradation through syndecan-4 in intervertebral disc. J Biol Chem. 2011;286:39738–39749.PubMedCentralPubMed

104.

Wang YT, Wu XT, Wang F. Regeneration potential and mechanism of bone marrow mesenchymal stem cell transplantation for treating intervertebral disc degeneration. J Orthop Sci. 2010;15:707–719.PubMed

105.

Woolf CJ, Ma QP, Allchorne A, Poole S. Peripheral cell types contributing to the hyperalgesic action of nerve growth factor in inflammation. J Neurosci. 1996;16:2716–2723.PubMed

106.

Yoshimura H, Muneta T, Nimura A, Yokoyama A, Koga H, Sekiya I. Comparison of rat mesenchymal stem cells de-rived from bone marrow, synovium, periosteum, adipose tissue, and muscle. Cell Tissue Res. 2007;327:449–462.PubMed

107.

Zhang Y, Proenca R, Maffei M, Barone M, Leopold L, Friedman JM. Positional cloning of the mouse obese gene and its human homologue. Nature. 1994;372:425–432.PubMed

108.

Zhao CQ, Liu D, Li H, Jiang LS, Dai LY. Expression of leptin and its functional receptor on disc cells: contribution to cell proliferation. Spine (Phila Pa 1976). 2008;33:E858–E864.

Titel: Molecular Basis of Intervertebral Disc Degeneration and Herniations: What Are the Important Translational Questions?
verfasst von: Tiffany Kadow, MD
Gwendolyn Sowa, MD, PhD
Nam Vo, PhD
James D. Kang, MD
Publikationsdatum: 01.06.2015
Verlag: Springer US
Erschienen in: Clinical Orthopaedics and Related Research® / Ausgabe 6/2015
Print ISSN: 0009-921X
Elektronische ISSN: 1528-1132
DOI: https://doi.org/10.1007/s11999-014-3774-8

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Patienten, die von Ärztinnen behandelt werden, dürfen offenbar auf bessere Therapieergebnisse hoffen als Patienten von Ärzten. Besonders gilt das offenbar für weibliche Kranke, wie eine Studie zeigt.

Notfall-TEP der Hüfte ist auch bei 90-Jährigen machbar

26.04.2024 Hüft-TEP Nachrichten

Ob bei einer Notfalloperation nach Schenkelhalsfraktur eine Hemiarthroplastik oder eine totale Endoprothese (TEP) eingebaut wird, sollte nicht allein vom Alter der Patientinnen und Patienten abhängen. Auch über 90-Jährige können von der TEP profitieren.

Arthroskopie kann Knieprothese nicht hinauszögern

25.04.2024 Gonarthrose Nachrichten

Ein arthroskopischer Eingriff bei Kniearthrose macht im Hinblick darauf, ob und wann ein Gelenkersatz fällig wird, offenbar keinen Unterschied.

Update Orthopädie und Unfallchirurgie

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Abstract

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