Intervertebral disc (IVD) disease (IDD) is a complex, multifactorial disease. While various aspects of IDD progression have been reported, the underlying molecular pathways and transcriptional networks that govern the maintenance of healthy nucleus pulposus (NP) and annulus fibrosus (AF) have not been fully elucidated. We defined the transcriptome map of healthy human IVD by performing single-cell RNA-sequencing (scRNA-seq) in primary AF and NP cells isolated from non-degenerated lumbar disc. Our systematic and comprehensive analyses revealed distinct genetic architecture of human NP and AF compartments and identified 2,196 differentially expressed genes. Gene enrichment analysis showed that SFRP1, BIRC5, CYTL1, ESM1 and CCNB2 genes were highly expressed in the AF cells; whereas, COL2A1, DSC3, COL9A3, COL11A1, and ANGPTL7 were mostly expressed in the NP cells. Further, functional annotation clustering analysis revealed the enrichment of receptor signaling pathways genes in AF cells, while NP cells showed high expression of genes related to the protein synthesis machinery. Subsequent interaction network analysis revealed a structured network of extracellular matrix genes in NP compartments. Our regulatory network analysis identified FOXM1 and KDM4E as signature transcription factor of AF and NP respectively, which might be involved in the regulation of core genes of AF and NP transcriptome.

Background: Rats are a widely accepted preclinical model for evaluating intervertebral disc (IVD) degeneration and regeneration. IVD morphology is commonly assessed using histology, which forms the foundation for quantifying the state of IVD degeneration. IVD degeneration severity is evaluated using different grading systems that focus on distinct degenerative features. A standard grading system would facilitate more accurate comparison across laboratories and more robust comparisons of different models and interventions.Aims: This study aimed to develop a histology grading system to quantify IVD degeneration for different rat models.

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Object The chronic stinger syndrome is a distinct entity from acute stingers and has been shown to have its own pathophysiology that, unlike acute stingers, may reflect long-standing geometrical changes of the subaxial spinal canal and chronic irritation/degeneration of the exiting nerve root complex. There is no method available, however, to accurately predict these symptoms in athletes. The mean subaxial cervical space available for the cord (MSCSAC) is a novel alternative to the Torg ratio for predicting neurological symptoms caused by cervical spondylosis in elite athletes. It is the goal of this study to determine critical values for this measurement index and to retrospectively correlate those values to neurological symptoms. Methods Magnetic resonance images obtained in 103 male athletes participating in the 2005 and 2006 National Football League Scouting Combine and a control group of 42 age-matched male nonathletes were retrospectively reviewed. The Torg ratio and SAC values were calculated in triplicate at each cervical level from C3–6 by using lateral radiographs and midsagittal T2-weighted MR images of the cervical spine, respectively. These values were then averaged for each individual to produce mean subaxial cervical Torg ratio (MSCTR) and MSCSAC values. Receiver operating characteristic curves were constructed for each measurement technique and were compared based on their respective area under the curves (AUCs). Results The MSCSAC difference between athletes with and without chronic stingers was statistically significant (p < 0.01). The difference between athletes with and without chronic stingers compared with controls was also statistically significant (p < 0.001 and p < 0.001, respectively). The AUC for the MSCSAC was 0.813, which was significantly greater than the AUC for both the MSCTR (p = 0.0475) and the individual Torg ratio (p = 0.0277). The MSCTR had the second largest AUC (0.676) and the conventional method of measuring individual Torg ratio values produced the lowest AUC (0.661). It was found that using the MSCSAC with a critical value of 5.0 mm produced a sensitivity of 80% and a negative likelihood ratio of 0.23 for predicting chronic stingers. Lowering the cutoff value to 4.3 mm for the MSCSAC resulted in a possible confirmatory test with a specificity of 96% and a positive likelihood ratio of 13.25. Conclusions A critical value of 5.0 mm for the MSCSAC provides the clinician with a screening test for chronic stingers and anything < 4.3 mm adds additional confidence as a confirmatory test. These results are ~ 20% more accurate than the classic Torg ratio based on our AUC analysis. It was found that measuring the spinal geometry throughout the length of the subaxial cervical spine produced a more reliable method by which to predict neurological symptoms than the traditional approach of measuring individual levels. This shows that the underlying pathogenesis of the chronic stinger syndrome is best characterized as a process that involves the entire subaxial region uniformly.