1. Andersson GB. Epidemiological features of chronic low-back pain. Lancet 1999;354:581-5.
2. Katz JN. Lumbar disc disorders and low-back pain: socioeconomic factors and consequences. J Bone Joint Surg Am 2006;88 Suppl 2(Suppl 2):21-4.
4. Urban JP, Roberts S. Degeneration of the intervertebral disc. Arthritis Res Ther 2003;5:120-30.
5. Saal JA, Saal JS. Nonoperative treatment of herniated lumbar intervertebral disc with radiculopathy. An outcome study. Spine (Phila Pa 1976) 1989;14:431-7.
6. Katz JN, Harris MB. Clinical practice. Lumbar spinal stenosis. N Engl J Med 2008;358:818-25.
7. Hunter CJ, Matyas JR, Duncan NA. The notochordal cell in the nucleus pulposus: a review in the context of tissue engineering. Tissue Eng 2003;9:667-77.
8. Alini M, Eisenstein SM, Ito K, et al. Are animal models useful for studying human disc disorders/degeneration? Eur Spine J 2008;17:2-19.
10. Poiraudeau S, Monteiro I, Anract P, et al. Phenotypic characteristics of rabbit intervertebral disc cells. Comparison with cartilage cells from the same animals. Spine (Phila Pa 1976) 1999;24:837-44.
11. Vo NV, Hartman RA, Yurube T, et al. Expression and regulation of metalloproteinases and their inhibitors in intervertebral disc aging and degeneration. Spine J 2013;13:331-41.
12. Kanemoto M, Hukuda S, Komiya Y, et al. Immunohistochemical study of matrix metalloproteinase-3 and tissue inhibitor of metalloproteinase-1 human intervertebral discs. Spine (Phila Pa 1976) 1996;21:1-8.
13. Roberts S, Caterson B, Menage J, et al. Matrix metalloproteinases and aggrecanase: their role in disorders of the human intervertebral disc. Spine (Phila Pa 1976) 2000;25:3005-13.
14. Pockert AJ, Richardson SM, Le Maitre CL, et al. Modified expression of the ADAMTS enzymes and tissue inhibitor of metalloproteinases 3 during human intervertebral disc degeneration. Arthritis Rheum 2009;60:482-91.
15. Yurube T, Nishida K, Suzuki T, et al. Matrix metalloproteinase (MMP)-3 gene up-regulation in a rat tail compression loading-induced disc degeneration model. J Orthop Res 2010;28:1026-32.
17. Hirata H, Yurube T, Kakutani K, et al. A rat tail temporary static compression model reproduces different stages of intervertebral disc degeneration with decreased notochordal cell phenotype. J Orthop Res 2014;32:455-63.
18. Nishida K, Kang JD, Gilbertson LG, et al. 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 (Phila Pa 1976) 1999;24:2419-25.
19. Urban JP, Smith S, Fairbank JC. Nutrition of the intervertebral disc. Spine (Phila Pa 1976) 2004;29:2700-9.
20. Yurube T, Buchser WJ, Moon HJ, et al. Serum and nutrient deprivation increase autophagic flux in intervertebral disc annulus fibrosus cells: an in vitro experimental study. Eur Spine J 2019;28:993-1004.
22. Boos N, Weissbach S, Rohrbach H, et al. Classification of age-related changes in lumbar intervertebral discs: 2002 Volvo Award in basic science. Spine (Phila Pa 1976) 2002;27:2631-44.
23. Cheung KM, Karppinen J, Chan D, et al. Prevalence and pattern of lumbar magnetic resonance imaging changes in a population study of one thousand forty-three individuals. Spine (Phila Pa 1976) 2009;34:934-40.
24. Fuchs Y, Steller H. Programmed cell death in animal development and disease. Cell 2011;147:1640.
25. Gruber HE, Hanley EN Jr. Analysis of aging and degeneration of the human intervertebral disc. Comparison of surgical specimens with normal controls. Spine (Phila Pa 1976) 1998;23:751-7.
27. Lombard DB, Chua KF, Mostoslavsky R, et al. DNA repair, genome stability, and aging. Cell 2005;120:497-512.
28. Gruber HE, Ingram JA, Norton HJ, et al. Senescence in cells of the aging and degenerating intervertebral disc: immunolocalization of senescence-associated beta-galactosidase in human and sand rat discs. Spine (Phila Pa 1976) 2007;32:321-7.
30. Ito M, Yurube T, Kakutani K, et al. Selective interference of mTORC1/RAPTOR protects against human disc cellular apoptosis, senescence, and extracellular matrix catabolism with Akt and autophagy induction. Osteoarthritis Cartilage 2017;25:2134-46.
31. Kakiuchi Y, Yurube T, Kakutani K, et al. Pharmacological inhibition of mTORC1 but not mTORC2 protects against human disc cellular apoptosis, senescence, and extracellular matrix catabolism through Akt and autophagy induction. Osteoarthritis Cartilage 2019;27:965-76.
34. Mizushima N, Levine B, Cuervo AM, et al. Autophagy fights disease through cellular self-digestion. Nature 2008;451:1069-75.
35. Hirsch C, Schajowicz F. Studies on structural changes in the lumbar annulus fibrosus. Acta Orthop Scand 1952;22:184-231.
36. Buckwalter JA. Aging and degeneration of the human intervertebral disc. Spine (Phila Pa 1976) 1995;20:1307-14.
37. Bydon M, De la Garza-Ramos R, Macki M, et al. Lumbar fusion versus nonoperative management for treatment of discogenic low back pain: a systematic review and meta-analysis of randomized controlled trials. J Spinal Disord Tech 2014;27:297-304.
38. Ghiselli G, Wang JC, Bhatia NN, et al. Adjacent segment degeneration in the lumbar spine. J Bone Joint Surg Am 2004;86:1497-503.
40. Sakai D, Andersson GB. Stem cell therapy for intervertebral disc regeneration: obstacles and solutions. Nat Rev Rheumatol 2015;11:243-56.
42. Wehling P, Schulitz KP, Robbins PD, et al. Transfer of genes to chondrocytic cells of the lumbar spine. Proposal for a treatment strategy of spinal disorders by local gene therapy. Spine (Phila Pa 1976) 1997;22:1092-7.
43. Nishida K, Kang JD, Suh JK, et al. Adenovirus-mediated gene transfer to nucleus pulposus cells. Implications for the treatment of intervertebral disc degeneration. Spine (Phila Pa 1976) 1998;23:2437. -42. discussion 2443.
44. Lattermann C, Oxner WM, Xiao X, et al. The adeno associated viral vector as a strategy for intradiscal gene transfer in immune competent and pre-exposed rabbits. Spine (Phila Pa 1976) 2005;30:497-504.
46. Lai CM, Lai YK, Rakoczy PE. Adenovirus and adeno-associated virus vectors. DNA Cell Biol 2002;21:895-913.
47. Liu X, Li K, Song J, et al. Efficient and stable gene expression in rabbit intervertebral disc cells transduced with a recombinant baculovirus vector. Spine (Phila Pa 1976) 2006;31:732-5.
50. Wallach CJ, Kim JS, Sobajima S, et al. Safety assessment of intradiscal gene transfer: a pilot study. Spine J 2006;6:107-12.
53. Lawrie A, Brisken AF, Francis SE, et al. Ultrasound enhances reporter gene expression after transfection of vascular cells in vitro. Circulation 1999;99:2617-20.
54. Newman CM, Lawrie A, Brisken AF, et al. Ultrasound gene therapy: on the road from concept to reality. Echocardiography 2001;18:339-47.
56. Nishida K, Doita M, Takada T, et al. Sustained transgene expression in intervertebral disc cells in vivo mediated by microbubble-enhanced ultrasound gene therapy. Spine (Phila Pa 1976) 2006;31:1415-9.
57. Harada A, Kataoka K. Formation of polyion complex micelles in an aqueous milieu from a pair of oppositely-charged block copolymers with poly (ethylene glycol) segments. Macromolecules 1995;28:5294-9.
58. Feng G, Zha Z, Huang Y, et al. Sustained and bioresponsive two-stage delivery of therapeutic miRNA via polyplex micelle-loaded injectable hydrogels for inhibition of intervertebral disc fibrosis. Adv Healthc Mater 2018;7:e1800623.
61. Cui M, Wan Y, Anderson DG, et al. Mouse growth and differentiation factor-5 protein and DNA therapy potentiates intervertebral disc cell aggregation and chondrogenic gene expression. Spine J 2008;8:287-95.
62. Liang H, Ma SY, Feng G, et al. Therapeutic effects of adenovirus-mediated growth and differentiation factor-5 in a mice disc degeneration model induced by annulus needle puncture. Spine J 2010;10:32-41.
63. Leckie SK, Bechara BP, Hartman RA, et al. 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.
66. Martinez J, Patkaniowska A, Urlaub H, et al. Single-stranded antisense siRNAs guide target RNA cleavage in RNAi. Cell 2002;110:563-74.
67. Schwarz DS, Hutvágner G, Haley B, et al. Evidence that siRNAs function as guides, not primers, in the drosophila and human RNAi pathways. Mol Cell 2002;10:537-48.
68. Hutvagner G, Zamore PD. A microRNA in a multiple-turnover RNAi enzyme complex. Science 2002;297:2056-60.
69. Kakutani K, Nishida K, Uno K, et al. Prolonged down regulation of specific gene expression in nucleus pulposus cell mediated by RNA interference in vitro. J Orthop Res 2006;24:1271-8.
71. Takada T, Nishida K, Doita M, et al. Fas ligand exists on intervertebral disc cells: a potential molecular mechanism for immune privilege of the disc. Spine (Phila Pa 1976) 2002;27:1526-30.
73. Sudo H, Minami A. Caspase 3 as a therapeutic target for regulation of intervertebral disc degeneration in rabbits. Arthritis Rheum 2011;63:1648-57.
74. Yamada K, Sudo H, Iwasaki K, et al. Caspase 3 silencing inhibits biomechanical overload-induced intervertebral disk degeneration. Am J Pathol 2014;184:753-64.
75. Lander ES. The heroes of CRISPR. Cell 2016;164:18-28.
76. Jansen R, Embden JD, Gaastra W, et al. Identification of genes that are associated with DNA repeats in prokaryotes. Mol Microbiol 2002;43:1565-75.
77. Barrangou R, Fremaux C, Deveau H, et al. CRISPR provides acquired resistance against viruses in prokaryotes. Science 2007;315:1709-12.
81. Farhang N, Ginley-Hidinger M, Berrett KC, et al. Lentiviral CRISPR epigenome editing of inflammatory receptors as a gene therapy strategy for disc degeneration. Hum Gene Ther 2019;30:1161-75.
82. Kabeya Y, Mizushima N, Ueno T, et al. LC3, a mammalian homologue of yeast Apg8p, is localized in autophagosome membranes after processing. EMBO J 2000;19:5720-8.
84. Zoncu R, Efeyan A, Sabatini DM. mTOR: from growth signal integration to cancer, diabetes and ageing. Nat Rev Mol Cell Biol 2011;12:21-35.
87. Chen JW, Ni BB, Zheng XF, et al. Hypoxia facilitates the survival of nucleus pulposus cells in serum deprivation by downregulating excessive autophagy through restricting ROS generation. Int. J. Biochem. Cell Biol 2015;59:1-10.
89. Ni BB, Li B, Yang YH, et al. The effect of transforming growth factor beta1 on the crosstalk between autophagy and apoptosis in the annulus fibrosus cells under serum deprivation. Cytokine 2014;70:87-96.