Mokdad, A. H. et al. The state of US health, 1990-2016. JAMA 319, 1444–1472 (2018).

Article  PubMed  PubMed Central  Google Scholar 

Katz, J. N. Lumbar disc disorders and low-back pain: socioeconomic factors and consequences. J. Bone Jt. Surg. Ser. A 88, 21–24 (2006).

Google Scholar 

Cheung, K. M. C. et al. Prevalence and pattern of lumbar magnetic resonance imaging changes in a population study of one thousand forty-three individuals. Spine (Philos. Pa 1976) 34, 934–940 (2009).

Article  Google Scholar 

Chou, R. et al. Diagnosis and treatment of low back pain: a joint clinical practice guideline from the American College of Physicians and the American Pain Society. Ann. Intern. Med. 147, 478–491 (2007).

Article  PubMed  Google Scholar 

Roberts, S., Evans, H., Trivedi, J. & Menage, J. Histology and pathology of the human intervertebral disc. J. Bone Jt. Surg. Ser. A 88, 10–14 (2006).

Google Scholar 

Airaksinen, O. et al. Chapter 4: European guidelines for the management of chronic nonspecific low back pain. Eur. Spine J. 15, S192–300 (2006).

Article  PubMed  PubMed Central  Google Scholar 

Dowdell, J. et al. Intervertebral disk degeneration and repair. Clin. Neurosurg. 80, S46–S54 (2017).

Article  Google Scholar 

Dvořák, J., Vajda, E. G., Grob, D. & Panjabi, M. M. Normal motion of the lumbar spine as related to age and gender. Eur. Spine J. 4, 18–23 (1995).

Article  PubMed  Google Scholar 

Adams, M. A. & Hutton, W. C. The effect of posture on the role of the apophysial joints in resisting intervertebral compressive forces. J. Bone Jt. Surg. Ser. B 62, 358–362 (1980).

Article  CAS  Google Scholar 

Huang, Y.-C., Urban, J. P. G. & Luk, K. D. K. Intervertebral disc regeneration: do nutrients lead the way? Nat. Rev. Rheumatol. 10, 1–6 (2014).

Article  Google Scholar 

Tsantrizos, A., Ito, K., Aebi, M. & Steffen, T. Internal strains in healthy and degenerated lumbar intervertebral discs. Spine (Philos. Pa 1976) 30, 2129–2137 (2005).

Article  Google Scholar 

Uematsu, Y., Matuzaki, H. & Iwahashi, M. Effects of nicotine on the intervertebral disc: an experimental study in rabbits. J. Orthop. Sci. 6, 77–82 (2001).

Article  Google Scholar 

Vo, N. et al. Differential effects of nicotine and tobacco smoke condensate on human annulus fibrosus cell metabolism. J. Orthop. Res. 29, 1585–1591 (2011).

Article  CAS  PubMed  Google Scholar 

Singh, D., Park, W., Hwang, D. & Levy, M. S. Severe obesity effect on low back biomechanical stress of manual load lifting. Work 51, 337–348 (2015).

Article  PubMed  Google Scholar 

Vadalà, G. et al. Early intervertebral disc degeneration changes in asymptomatic weightlifters assessed by T1ρ’ -magnetic resonance imaging. Spine (Philos. Pa 1976) 39, 1881–1886 (2014).

Article  Google Scholar 

UN. World Population Prospects 2019 (Department of Economic and Social Affairs, 2019).

Munir, S. et al. Endplate defect is heritable, associated with low back pain and triggers intervertebral disc degeneration: a longitudinal study from Twinsuk. Spine (Philos. Pa 1976) 43, 1496–1501 (2018).

Article  Google Scholar 

Battié, M. C. et al. The twin spine study: contributions to a changing view of disc degeneration. Spine J. 9, 47–59 (2009).

Article  PubMed  Google Scholar 

Toktaş, Z. O. et al. Association of collagen I, IX and vitamin D receptor gene polymorphisms with radiological severity of intervertebral disc degeneration in Southern European Ancestor. Eur. Spine J. 24, 2432–2441 (2015).

Article  PubMed  Google Scholar 

Takahashi, M. et al. The association of degeneration of the intervertebral disc with 5a/6a polymorphism in the promoter of the human matrix metalloproteinase-3 gene. J. Bone Jt. Surg. Ser. B 83, 491–495 (2001).

Article  CAS  Google Scholar 

Huang, X. et al. Interleukin 6 (IL-6) and IL-10 promoter region polymorphisms are associated with risk of lumbar disc herniation in a Northern Chinese han population. Genet. Test. Mol. Biomark. 21, 17–23 (2017).

Article  CAS  Google Scholar 

Guerin, H. L. & Elliott, D. M. Quantifying the contributions of structure to annulus fibrosus mechanical function using a nonlinear, anisotropic, hyperelstic model. J. Orthop. Res. 25, 508–516 (2007).

Article  PubMed  Google Scholar 

O’Connell, G. D., Jacobs, N. T., Sen, S., Vresilovic, E. J. & Elliott, D. M. Axial creep loading and unloaded recovery of the human intervertebral disc and the effect of degeneration. J. Mech. Behav. Biomed. Mater. 4, 933–942 (2011).

Article  PubMed  PubMed Central  Google Scholar 

Roberts, S. Disc morphology in health and disease. Biochem. Soc. Trans. 30, 864–869 (2002).

Article  CAS  PubMed  Google Scholar 

Chanchairujira, K. et al. Intervertebral disk calcification of the spine in an elderly population: radiographic prevalence, location, and distribution and correlation with spinal degeneration. Radiology 230, 499–503 (2007).

Article  Google Scholar 

Boos, N. et al. Classification of age-related changes in lumbar intervertebral discs: 2002 Volvo Award in basic science. Spine (Philos. Pa 1976) 27, 2631–2644 (2002).

Article  Google Scholar 

Novais, E. J. et al. Comparison of inbred mouse strains shows diverse phenotypic outcomes of intervertebral disc aging. Aging Cell 19, e13148 (2020).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Yee, A. et al. Fibrotic-like changes in degenerate human intervertebral discs revealed by quantitative proteomic analysis. Osteoarthr. Cartil. 24, 503–13 (2016).

Article  CAS  Google Scholar 

Roberts, S., Bains, M. A., Kwan, A., Menage, J. & Eisenstein, S. M. Type X collagen in the human invertebral disc: an indication of repair or remodelling? Histochem. J. 30, 89–95 (1998).

Article  CAS  PubMed  Google Scholar 

Vo, N. et al. Accelerated aging of intervertebral discs in a mouse model of progeria. J. Orthop. Res. 28, 1600–1607 (2010).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Bachmeier, B. E. et al. Matrix metalloproteinase expression levels suggest distinct enzyme roles during lumbar disc herniation and degeneration. Eur. Spine J. 18, 1573–1586 (2009).

Article  PubMed  PubMed Central  Google Scholar 

Hristova, G. I. et al. Calcification in human intervertebral disc degeneration and scoliosis. J. Orthop. Res. 29, 1888–95 (2011).

Article  PubMed  Google Scholar 

Shao, J. et al. Differences in calcification and osteogenic potential of herniated discs according to the severity of degeneration based on Pfirrmann grade: a cross-sectional study. BMC Musculoskelet. Disord. 17, 191 (2016).

Article  PubMed  PubMed Central  Google Scholar 

Teraguchi, M. et al. Prevalence and distribution of intervertebral disc degeneration over the entire spine in a population-based cohort: the Wakayama Spine Study. Osteoarthr. Cartil. 22, 104–110 (2014).

Article  CAS  Google Scholar 

Zehra, U. et al. Mechanisms and clinical implications of intervertebral disc calcification. Nat. Rev. Rheumatol. 18, 352–362 (2022).

Article  PubMed  PubMed Central  Google Scholar 

Bangert, B. A. et al. Hyperintense disks on T1-weighted MR images: correlation with calcification. Radiology 195, 437–443 (1995).

Article  CAS  PubMed  Google Scholar 

Weinberger, A. & Myers, A. R. Intervertebral disc calcification in adults: a review. Semin. Arthritis Rheum. 8, 69–75 (1978).

Article  CAS  PubMed  Google Scholar 

Stigen, Ø., Ciasca, T. & Kolbjørnsen, Ø. Calcification of extruded intervertebral discs in dachshunds: a radiographic, computed tomographic and histopathological study of 25 cases. Acta Vet. Scand. 61, 13 (2019).

Article  PubMed  PubMed Central  Google Scholar 

Park, J. et al. Dual pathways to endochondral osteoblasts: a novel chondrocyte-derived osteoprogenitor cell identified in hypertrophic cartilage. Biol. Open 4, 608–621 (2015).

Article  PubMed  PubMed Central  Google Scholar 

Jin, L. et al. Annulus fibrosus cell characteristics are a potential source of intervertebral disc pathogenesis. PLoS One 9, e96519 (2014).

Article  PubMed  PubMed Central  Google Scholar 

Zhao, Y. P. et al. Progranulin knockout accelerates intervertebral disc degeneration in aging mice. Sci. Rep. 5, 9102 (2015).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Stokes, I. A. F. & Iatridis, J. C. Mechanical conditions that accelerate intervertebral disc degeneration: Overload versus immobilization. Spine 29, 2724–2732 (2004).

Article  PubMed  PubMed Central  Google Scholar 

Roberts, S., Menage, J. & Eisenstein, S. M. The cartilage end‐plate and intervertebral disc in scoliosis: calcification and other sequelae. J. Orthop. Res. 11, 747–757 (1993).

Article  CAS  PubMed