The Key Laboratory of Molecular Biology, State Administration of Traditional Chinese Medicine, School of Traditional Chinese Medicine, Southern Medical University, Guangzhou 510515, China ; Department of Pharmacology, Guangdong Key Laboratory for R&D of Natural Drug, Guangdong Medical College, Zhanjiang 524023, China.
Department of Pharmacology, Guangdong Key Laboratory for R&D of Natural Drug, Guangdong Medical College, Zhanjiang 524023, China.
Oxid Med Cell Longev. 2013;2013:351895. doi: 10.1155/2013/351895. Epub 2013 Dec 31.
There is now increasing evidence which suggests a pivotal role for oxidative stress in the development and progression of osteoporosis. We confirm herein the protective effects of natural antioxidant Tanshinol against oxidative stress in osteoblastic differentiation and the underlying mechanism. Our results show that hydrogen peroxide (H2O2) leads to accumulation of reactive oxygen species (ROS), decrease in cell viability, cell cycle arrest and apoptosis in a caspase-3-dependent manner, and inhibition of osteoblastic differentiation. Tanshinol reverses these deleterious consequence triggered by oxidative stress. Moreover, under the condition of oxidative stress, Tanshinol suppresses the activation of FoxO3a transcription factor and expressions of its target genes Gadd45a and catalase (CAT) and simultaneously counteracts the inhibition of Wnt signalling and expressions of target genes Axin2, alkaline phosphatase (ALP), and Osteoprotegerin (OPG). The findings are further consolidated using FoxO3a siRNA interference and overexpression of Tcf4. The results illustrate that Tanshinol attenuates oxidative stress via down-regulation of FoxO3a signaling, and rescues the decrease of osteoblastic differentiation through upregulation of Wnt signal under oxidative stress. The present findings suggest that the beneficial effects of Tanshinol may be adopted as a novel therapeutic approach in recently recognized conditions of niche targeting osteoporosis.
现在有越来越多的证据表明，氧化应激在骨质疏松症的发生和发展中起着关键作用。我们在此证实了天然抗氧化剂丹参醇在成骨细胞分化中对抗氧化应激的保护作用及其潜在机制。我们的结果表明，过氧化氢（H2O2）导致活性氧（ROS）积累，细胞活力下降，细胞周期停滞和 caspase-3 依赖性细胞凋亡，并抑制成骨细胞分化。丹参醇逆转了氧化应激引起的这些有害后果。此外，在氧化应激条件下，丹参醇抑制 FoxO3a 转录因子的激活及其靶基因 Gadd45a 和过氧化氢酶（CAT）的表达，同时抵消 Wnt 信号的抑制和靶基因 Axin2、碱性磷酸酶（ALP）和骨保护素（OPG）的表达。使用 FoxO3a siRNA 干扰和 Tcf4 的过表达进一步证实了这些发现。结果表明，丹参醇通过下调 FoxO3a 信号减轻氧化应激，并通过上调 Wnt 信号在氧化应激下挽救成骨细胞分化的减少。这些发现表明，丹参醇的有益作用可能被采用作为最近认识到的针对骨质疏松症龛位的新型治疗方法。
