The effect of vitamin K insufficiency on histological and structural properties of knee joints in aging mice

Abstract

While a role for vitamin K in maintaining joint tissue homeostasis has been proposed based on the presence of vitamin K dependent proteins in cartilage and bone, it is not clear if low vitamin K intake is causally linked to joint tissue degeneration. To address this gap, we manipulated vitamin K status in aging mice to test its effect on age-related changes in articular cartilage and sub-chondral bone. Eleven-month old male C57BL6 mice were randomly assigned to a low vitamin K diet containing 120 mcg phylloquinone/kg diet (n=32) or a control diet containing 1.5mg phylloquinone/kg diet (n=30) for 6 months. Knees were evaluated histologically using Safranin O and H&E staining, as well as using micro-CT. Eleven mice in the low vitamin K diet group and three mice in the control group died within the first 100 days of the experiment (p=0.024). Mice fed the low vitamin K diet had higher Safranin-O scores, indicative of more proteoglycan loss, compared to mice fed the control diet (p≤0.026). The articular cartilage structure scores did not differ between the two groups (p≥0.190). The sub-chondral bone parameters measured using micro CT also did not differ between the two groups (all p≥0.174). Our findings suggest low vitamin K status can promote joint tissue proteoglycan loss in older male mice. Future studies are needed to confirm our findings and obtain a better understanding of the molecular mechanisms underlying the role of vitamin K in joint tissue homeostasis.