A histocytological and radiological overview of the natural history of intervertebral disk: from embryonic formation to age-related degeneration



To elucidate the natural history of intervertebral disk (IVD) and characterize its embryonic beginnings and age-related degeneration.


Coronal sections of embryonic (E13.5-neonatal) and postnatal (4–60-week-old) Sprague–Dawley rat IVD were stained by a series of histological stainings (hematoxylin and eosin, Alcian blue, Picrosirius red, Masson, Periodic acid–Schiff). Growth kinetics within embryonic IVD were evaluated by immunohistochemical staining of Ki67 and proliferating cell nuclear antigen. Postnatal maturation and degeneration of IVD were visualized on radiology by X-ray, CT, and MR imaging.


During the formation of rat IVD, inner annulus fibrosus (AF) and cartilaginous endplate (CEP) shared similar cell density, extracellular matrix, and potential of growth kinetics; notochord provided increased and enlarged cytoplasmic vacuoles to generate nucleus pulposus (NP), part of which was retained within CEP. Postnatally, vacuolated notochord cells were reduced by devacuolation, while chondrocytic NP cells increased; cartilaginous layers of CEP were narrowed by vertebrae growth and secondary ossification; fibrotic portion of AF decreased as cartilaginous matrix accumulated and infiltrated outward. In aged and degenerated IVD, large longitudinal fissures were detected near the boundaries between inner and outer AF, whereas both reduced cellularity and accumulated cell clusters were evident within the dehydrated NP; only part of these histocytological changes could be reported on radiology.


By showing that the natural history of IVD is orchestrated by a dynamic histocytological regulation, our study may facilitate better understanding of the developmental defects, cellular heterogeneity, age-related degenerative mechanisms, and biological regeneration of IVD.

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This study was supported by the National Natural Science Foundation of China (No. 81201423, No. 81272035, No. 81572170) and the Fundamental Research Funds of the Central Universities (No. 2242017K3DN06). The authors would like to acknowledge He-Ling Fu, Yuan Zheng, and Dan Bao, from the Animal Core facility of Nanjing Medical University, for their aids in radiological imaging and analysis.

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Correspondence to Xiao-Tao Wu.

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Wang, F., Zhang, C., Sinkemani, A. et al. A histocytological and radiological overview of the natural history of intervertebral disk: from embryonic formation to age-related degeneration. Eur Spine J 28, 633–648 (2019). https://doi.org/10.1007/s00586-019-05903-8

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  • Intervertebral Disk
  • Embryogenesis
  • Cytoplasmic Vacuole
  • Notochord
  • Sclerotome