Secreted chemokines and transcriptomic analyses reveal diverse inflammatory and degenerative processes in the intervertebral disc of the STZ-HFD mouse model of Type 2 diabetes

The chronic inflammation resultant from type 2 diabetes (T2D) is also associated with spinal pathologies, including intervertebral disc (IVD) degeneration and chronic neck and back pain. Although confounding factors, such as increased weight gain in obesity, studies have shown that even after adjusting age, body mass index, and genetics (e.g. twins), patients with T2D suffer from disproportionately more IVD degeneration and back pain. We hypothesize that chronic T2D fosters a proinflammatory microenvironment within the IVD that promotes degeneration and disrupts disc homeostasis. To test this hypothesis, we evaluated two commonly used mouse models of T2D – the leptin-receptor deficient mouse (db/db) and the chronic high-fat diet in mice with impaired beta-cell function (STZ-HFD). STZ-HFD IVDs were more degenerated and showed differential expression of chemokines from the db/db models. Moreover, the RNAseq analysis revealed vast transcriptional dysregulation of many pathways in the STZ-HFD but not in the db/db tissues. Taken together, the STZ-HFD may better recapitulates the complexities of the chronic inflammatory processes in the IVD during T2D Overall design: Samples were derived from two cohorts. Cohort 1 is 3 db/db mice and 3 db/+ heterozygous mice as non-diabetic controls. Cohort 2 is 4 Streptozocin-High-Fat-Diet diabetic mice with 4 healthy wild-type C57BL/6J mice as control. Intervertebral discs were extracted, pulverized, and reconstiuted in TRIzol prior to RNA extraction via column extraction in accordance with manufacturer recommendation. RNA in H2O were submitted to the WashU in St Louis GTAC core for Illumina NovaSeq X Plus Analysis.