Intervertebral disc (IVD) degeneration and associated low back pain (LBP) is a persistent condition experienced by 80% of individuals at some time in their lifespan. LBP has been the leading cause of years lived with disability worldwide since 1990 and remains a significant global public health concern. IVD degeneration happens when there is a loss of function of the intervertebral disc. Those discs are the shock-absorbing structure between each vertebra to provide spine flexibility. It is important to determine when there is a loss of function to prevent the development of LBP. It can be possible by identifying biomarkers of IVD degeneration.
goal
Biological markers or simply ‘biomarkers’ are important to help identify and diagnose a medical condition or a biological state. Examples can be the levels of certain substances in the blood, in the urine or in different tissues that may or may not change over time depending on the progression of the disease. Better understanding this condition by studying biomarkers can help the development of diagnostic and therapeutic options. The goal of this study is to identify new specific biomarkers and to characterize the observable characteristics and abundance of distinct cell populations in the degenerate and non-degenerate human disc tissue.
methodology
Dr Haglund research team used a specific technique called ‘single-cell RNA sequencing’ or ‘sc-RNA-seq’ to examine the gene expression in disc cells, both in anatomically distinct regions and for comparisons with pathology. Cells were isolated rapidly and immediately prepared for RNA-sequencing. This technique has potential to reveal the endogenous or internal gene expression of resident cells and thus identify individual cell differences in the native disc. Genetic analyses were used to discover molecular functions, biological processes, and transcription factors which control the rate of gene expression linked to both cell type and degeneration state. Protein and total gene expression of selected genes validated the findings.
main findings
Results of sc-RNA-seq from degenerate and non-degenerate human disc tissues rely on mapping cells with similar gene expression profiles into ‘clusters’ in order to name and number discrete cell populations in the human disc. Mapping cells will allow to identify the interactions that happen within cells based on the genes and proteins that are expressed. This approach allowed the research team to identify relationships between identified clusters and primary cell functions of matrix regulation, stress responses, cell cycle and more. Specifically, the research team propose a list of specific cell-type biomarkers and a list of predictive intervertebral disc degeneration genes.
take home message
This study reveals new insights into disc cell phenotypes and potential biomarkers of intervertebral disc degeneration and low back pain. These findings provide the basis for future work to understand the disc cell specificity in mediating the progression of intervertebral disc degeneration and the related low back pain and thus great promise for improving diagnostic and therapeutic possibilities.
