Intervertebral Disc Degeneration Is Associated With Aberrant Endplate Remodeling and Reduced Small Molecule Transport

Abstract

The intervertebral disc is the largest avascular structure in the body, and cells within the disc rely on diffusive transport via vasculature located within the vertebral endplate to receive nutrients, eliminate waste products, and maintain disc health. However, the mechanisms by which small molecule transport into the disc occurs in vivo and how these parameters change with disc degeneration remain understudied. Here, we utilize an in vivo rabbit puncture disc degeneration model to study these interactions and provide evidence that remodeling of the endplate adjacent to the disc occurs concomitant with degeneration. Our results identify significant increases in endplate bone volume fraction, increases in microscale stiffness of the soft tissue interfaces between the disc and vertebral bone, and reductions in endplate vascularity and small molecule transport into the disc as a function of degenerative state. A neural network model identified changes in diffusion into the disc as the most significant predictor of disc degeneration. These findings support the critical role of trans-endplate transport in disease progression and will improve patient selection to direct appropriate surgical intervention and inform new therapeutic approaches to improve disc health.

Plasma Rich in Growth Factors (PRGF) in the Treatment of Cervical and Lumbar Back Pain: A Retrospective Observational Clinical Study

“…Recent studies support the hypothesis of a global approach to back pain pathologies, since changes in the vertebral bone, especially in the endplates, influence the transport of nutrients to the disc and its eventual degeneration (35). The appropriate crosstalk between the IVD and the subchondral bone is a key feature of the homeostasis of the intervertebral joint functional unit (IVD, the upper and lower vertebrae, and the facet joints) (17).…”

Development of a standardized histopathology scoring system for intervertebral disc degeneration and regeneration in rabbit models‐An initiative of the ORSspine section

“…The Masuda scoring system for disc degeneration included categories for characterizing changes to the AF and NP, but did not include scoring of the EP to assess cartilage and bony EP remodeling, or scoring for cellular changes occurring with regeneration which provides information on the biological action of regenerative strategies. Scoring of these features was therefore included in the proposed scoring system, modified from scoring systems utilized by Chujo et al 18 and Ashinsky et al 20 Because the use of decalcified, paraffin processed sections is recommended for scoring, the endplate features included in the scoring system are focused solely on morphologic changes to this region. Researchers interested in studying alterations in calcification of this region would need to employ alternative methods, such as microcomputed tomography or cryo‐ or plastic sectioning to quantify or visualize endplate calcification.…”

Carbohydrate sulfotransferase 3 (CHST3) overexpression promotes cartilage endplate‐derived stem cells (CESCs) to regulate molecular mechanisms related to repair of intervertebral disc degeneration by rat nucleus pulposus

“…Degenerative intervertebral disc is a kind of hypoxia, nutrient deficiency, slightly acidic, high osmotic pressure, high mechanical stress of the poor internal environment. Puluqiao et al found that the apoptosis of CESCs increased and the expression of apoptosis‐related proteins BNIP3, Bax and Bak upregulated under the condition of hypoxia and nutrient deficiency 20,21 . He et al found that low nutrient environment can induce high expression of BNIP3 protein in CESCs and induce apoptosis of CESCs through BNIP3 related signal pathway 22 .…”