Shea M Kyla, Booth Sarah L, Harshman Stephanie G, Smith Donald, Carlson Cathy S, Harper Lindsey, Armstrong Alexandra R, Fang Min, Cancela M Leonor, Loeser Richard F
USDA Human Nutrition Research Center on Aging at Tufts University, Boston MA, USA.
College of Veterinary Medicine, University of Minnesota, St. Paul MN, USA.
Osteoarthr Cartil Open. 2020 Jun 2;2(3):100078. doi: 10.1016/j.ocarto.2020.100078. eCollection 2020 Sep.
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 1.5 mg 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.
虽然基于软骨和骨骼中存在维生素K依赖蛋白，有人提出维生素K在维持关节组织稳态中发挥作用，但目前尚不清楚低维生素K摄入量是否与关节组织退变存在因果关系。为填补这一空白，我们对衰老小鼠的维生素K状态进行调控，以测试其对关节软骨和软骨下骨年龄相关变化产生的影响。
将11月龄雄性C57BL6小鼠随机分为两组，一组给予含120微克叶绿醌/千克饲料的低维生素K饮食（n = 32），另一组给予含1.5毫克叶绿醌/千克饲料的对照饮食（n = 30），持续6个月。使用番红O和苏木精-伊红染色以及微型计算机断层扫描对膝关节进行组织学评估。
低维生素K饮食组的11只小鼠和对照组的3只小鼠在实验的前100天内死亡（p = 0.024）。与喂食对照饮食的小鼠相比，喂食低维生素K饮食的小鼠番红O评分更高，表明蛋白聚糖损失更多（p≤0.026）。两组之间的关节软骨结构评分没有差异（p≥0.190）。使用微型计算机断层扫描测量得到的软骨下骨参数在两组之间也没有差异（所有p≥0.174）。
我们的研究结果表明，低维生素K状态会促进老年雄性小鼠关节组织蛋白聚糖的流失。未来需要开展进一步研究以证实我们的发现，并更好地理解维生素K在关节组织稳态中发挥作用的分子机制。
