**Background:** Intervertebral disc degeneration (IVDD) is a major cause of low back pain and is frequently associated with type 2 diabetes mellitus (T2DM). The pathogenesis of IVDD in T2DM is not fully understood, and the potential influence of vitamin K2 (vit. K2) on this process has not been explored. Vitamin K2 is known for its anti-inflammatory, antioxidant, and bone-protective properties, and it may affect glucose metabolism. This study aimed to investigate the effect of a vit. K2-MK7 diet on IVD histopathology and IVD cell phenotype in a T2DM rat model, and to analyze the expression of cartilage-specific components, IL-10 family cytokines, and cell-stress-related markers.
**Methods:** The study used male Zucker Diabetes Fatty (ZDF) rats, including non-diabetic heterozygous (fa/+) and diabetic homozygous (fa/fa) animals. Four groups were formed: non-diabetic without vit. K2, non-diabetic with vit. K2, diabetic without vit. K2, and diabetic with vit. K2. Vit. K2 (MK-7) was mixed into the diet at 100 mg/kg and fed to 95-110-day-old rats for 80 days. Lumbar motion segments were harvested for histopathological analysis using hematoxylin-eosin, Alcian blue, and Sirius red staining. IVD degeneration was scored using an adapted Rutges scoring system (0-14 scale). Femur lengths and vertebral epiphyseal cross-section areas were measured. IVD fibrochondrocytes were isolated and cultured for immunofluorescence labeling (collagen types 1 and 2, aggrecan, decorin, SOX9, IL-10, IL-24, αSMA) and quantitative real-time PCR (Acan, Col1a1, Col2a1, Cd55, Cd59, Hmox1, Socs3). Statistical analysis used one-way ANOVA with Tukey's post-hoc test (significance at p ≤ 0.05).
**Key Results:** Diabetic rats exhibited typical T2DM features (polydipsia, polyphagia, hyperglycemia, obesity). Femur lengths were significantly shorter in diabetic rats compared to non-diabetic rats, with no effect from vit. K2. Epiphyseal cross-section areas were also smaller in diabetic rats. Histopathological scoring showed significantly higher IVD degeneration in diabetic animals (mean scores higher) compared to controls, with the difference being significant (p values not explicitly stated for all comparisons, but Figure 3 indicates significance). Vit. K2 did not significantly alter the degeneration scores. In cultured IVD cells, collagen type 1 and 2 protein expression showed no significant differences between groups, though there was a trend of higher collagen type 1 in diabetic animals without vit. K2. Aggrecan protein and gene expression tended to be lower in diabetic rats, especially with vit. K2. IL-10 and IL-24 protein expression showed no significant differences, but IL-10 trended higher in diabetic animals without vit. K2. αSMA protein expression was higher in cells from vit. K2-treated animals (both non-diabetic and diabetic). Gene expression of Socs3 and Hmox1 was highest in cells from diabetic animals treated with vit. K2, though not statistically significant. Cd55 and Cd59 gene expression showed an inductive trend in diabetic animals with vit. K2.
**Clinical Implications:** This study confirms a link between T2DM and IVDD in a rat model, supporting the hypothesis that diabetes contributes to disc degeneration. The finding of shorter femurs in diabetic rats suggests a potential effect of diabetes on bone growth, possibly through metabolic disturbances affecting epiphyseal plates. Vitamin K2 supplementation did not prevent IVDD or femoral shortening, but it did influence the expression of stress-associated markers (Socs3, Hmox1) and αSMA in IVD cells, indicating a possible modulatory role in cellular stress responses. However, the lack of significant effects on histopathology and major ECM components suggests that vit. K2 may not be a strong therapeutic agent for IVDD in the context of T2DM. The study highlights the need for further research to clarify the roles of IL-10 and IL-24 in IVDD and to explore the potential of vit. K2 in modulating inflammatory and oxidative stress pathways. The findings underscore the importance of managing T2DM to potentially mitigate IVDD progression.