Conclusions
Deletion of Sox9 in Aggrecan-expressing IVD tissues affects disc degeneration and associated pain behaviors through the β-catenin-CCL2 pathway. Such findings can lead to more targeted, personalized therapeutics in the future to address discogenic origins of LBP.
Methods
This study utilized Agc1-CreERT2;Sox9 flox/flox mice to investigate the effects of SOX9 deletion on IVD degeneration and associated pain behaviors. Mice were administered tamoxifen to induce conditional gene deletion of Sox9. Structural and degenerative phenotypes of the spine were assessed by a histological scoring system and micro-computed tomography (microCT). Pain behaviors were evaluated through mechanical allodynia testing and the LABORAS system for spontaneous behavior assessment. Immunohistochemistry identified the expression of proteins of interest, which were further examined by Western blotting. Lastly, quantitative real-time PCR and promoter assays on IVD cells were used to examine inflammatory and signaling pathways induced by Sox9 deletion.
Results
Crossing Agc1-CreERT2 mice with Sox9 flox/flox mice revealed that Sox9 conditional deletion (Sox9 cKO ) in cartilage tissues causes IVD degeneration and pain behavior. Sox9 cKO mice spines had narrowed intervertebral disc spaces and disorganized IVD tissues. Sox9 deletion also increased β-catenin, C-C motif chemokine ligand 2 (CCL2), and Glial cell line-derived neurotrophic factor (GDNF) expression in the IVD, suggesting their roles in disc pain and degeneration and the importance of the β-catenin/CCL2 pathway in these processes. Conclusions: Deletion of Sox9 in Aggrecan-expressing IVD tissues affects disc degeneration and associated pain behaviors through the β-catenin-CCL2 pathway. Such findings can lead to more targeted, personalized therapeutics in the future to address discogenic origins of LBP.