Deng Lili, Ding Yuedi, Peng Ying, Wu Yu, Fan Jun, Li Wenxin, Yang Runlin, Yang Meiling, Fu Qiang
Key Laboratory of Nuclear Medicine, Ministry of Health, Jiangsu Key Laboratory of Molecular Nuclear Medicine, Jiangsu Institute of Nuclear Medicine, Wuxi, Jiangsu, China.
Key Laboratory of Nuclear Medicine, Ministry of Health, Jiangsu Key Laboratory of Molecular Nuclear Medicine, Jiangsu Institute of Nuclear Medicine, Wuxi, Jiangsu, China.
Bone. 2014 Oct;67:200-7. doi: 10.1016/j.bone.2014.07.006. Epub 2014 Jul 11.
γ-Tocotrienol (GT3), an analogue of vitamin E, has gained increasing scientific interest recently as it provides significant health benefits. GT3 exerts its biological effects not only by virtue of antioxidant properties but also by inhibiting hydroxy-methyl-glutaryl-coenzyme A (HMG-CoA) reductase. Studies have reported that the mevalonate pathway is relevant for bone metabolism and HMG-CoA reductase inhibitors can increase bone mass and are useful in osteoporosis therapy. However, whether it is involved in the bone anabolic activity of GT3 is not clear. This study was conducted to investigate the ability of GT3 to protect against ovariectomy-induced bone loss, as well as the correlation between the protections and mevalonate pathway. Results showed that mice supplemented with 100mg/kg emulsified GT3 via subcutaneous injection once per month for three months were significantly protected from ovariectomy-induced bone loss as evaluated by various bone structural parameters, bone metabolic gene expression levels and serum levels of biochemical markers for bone resorption and bone formation. Importantly, the effect of GT3 on preventing against ovariectomy-induced bone loss could be reversed by daily supplementation with mevalonate, indicating that GT3 may via an HMG-CoA reductase-dependent mechanism to protect against ovariectomy-induced bone loss. Our results suggest that GT3 is suitable as dietary supplement and has potential as an alternative drug to treat or prevent osteoporosis.
γ-生育三烯酚（GT3）是维生素E的类似物，近来已引起越来越多的科学关注，因为它具有显著的健康益处。GT3不仅凭借抗氧化特性发挥其生物学效应，还通过抑制羟甲基戊二酰辅酶A（HMG-CoA）还原酶发挥作用。研究报告称，甲羟戊酸途径与骨代谢相关，HMG-CoA还原酶抑制剂可增加骨量，对骨质疏松症治疗有用。然而，它是否参与GT3的骨合成代谢活性尚不清楚。本研究旨在调查GT3预防去卵巢诱导的骨质流失的能力，以及这种保护作用与甲羟戊酸途径之间的相关性。结果表明，通过每月皮下注射一次100mg/kg乳化GT3，持续三个月的小鼠，经各种骨结构参数、骨代谢基因表达水平以及骨吸收和骨形成生化标志物的血清水平评估，显著预防了去卵巢诱导的骨质流失。重要的是，GT3预防去卵巢诱导的骨质流失的作用可通过每日补充甲羟戊酸来逆转，这表明GT3可能通过HMG-CoA还原酶依赖性机制预防去卵巢诱导的骨质流失。我们的结果表明，GT3适合作为膳食补充剂，并且有潜力作为治疗或预防骨质疏松症的替代药物。
