Curcumin alleviates glucocorticoid-induced osteoporosis through the regulation of the Wnt signaling pathway.
Curcumin alleviates glucocorticoid-induced osteoporosis through the regulation of the Wnt signaling pathway.
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姜黄素通过调节Wnt信号通路减轻糖皮质激素引起的骨质疏松
DOI：
10.3892/ijmm.2015.2432
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发表时间：
2016-02
影响因子：
5.4
通讯作者：
Fu Q
中科院分区：
文献类型：
--
作者：
Chen Z;Xue J;Shen T;Mu S;Fu Q
众所周知，糖皮质激素(GC)长期治疗会导致骨质疏松症。本研究旨在评价姜黄素对地塞米松(DXM)所致骨质疏松大鼠骨骼的保护作用。在本研究中，给大鼠灌胃地塞米松60天，造成骨质疏松，然后再给予姜黄素(100 mg/kg/d)治疗60天。H&E染色观察股骨的病理变化。检测血清骨钙素水平和I型胶原片段(CTX)作为骨代谢标志物。结果表明，姜黄素治疗可减轻DXM所致的股骨骨损伤，升高血清骨钙素水平，降低CTX水平。此外，在体外实验中，用0.5、1和2µM的姜黄素处理原代大鼠成骨细胞，并将其暴露于100 NM的地塞米松。用四甲基偶氮唑盐比色法检测细胞的增殖能力。检测碱性磷酸酶活性和转录因子2(Runx2)、Osterix、骨钙素、胶原、1型、α1(Col1A1)和骨连接蛋白的mRNA表达水平，以评估转录因子相关的成骨分化。检测护骨素(OPG)和核因子-kappaB受体激活剂(RANKL)的mRNA和蛋白表达水平，以评价细胞因子相关的破骨细胞的形成。结果表明，姜黄素以剂量依赖方式拮抗地塞米松对成骨细胞增殖能力的抑制作用。此外，姜黄素还上调了有利于成骨细胞分化的转录因子的mRNA表达水平，并增加了OPG/RANKL的比例。此外，还研究了姜黄素对Wnt信号通路的影响。RT-qPCR和Western印迹分析表明，被DXM抑制的Wnt信号通路在姜黄素处理后被重新激活。免疫荧光染色显示姜黄素可恢复地塞米松刺激的成骨细胞β-连环蛋白的核内染色。总之，我们的数据表明，姜黄素可能是一种潜在的治疗GC诱导的骨质疏松症的药物。
It is known that prolonged glucocorticoid (GC) treatment results in osteoporosis. This study aimed to evaluate the protective effects of curcumin on the bones of rats with dexamethasone (DXM)-induced osteoporosis. In the present study, rats were administered DXM for 60 days to induce osteoporosis, and they were then treated with curcumin (100 mg/kg/day) for a further 60 days. H&E staining was used to observe the pathological changes in the femurs. Serum osteocalcin levels and collagen-type I fragments (CTX) were examined as bone metabolism markers. The results revealed that treatment with curcumin attenuated DXM-induced bone injury in femurs, increased the serum levels of osteocalcin and decreased the levels of CTX. In addition, in in vitro experiments, primary rat osteoblasts treated with curcumin at 0.5, 1 and 2 µM were exposed to 100 nM DXM. An MTT assay was used to determine the proliferative ability of the cells. Alkaline phosphatase activity, and the mRNA expression levels of runt-related transcription factor 2 (Runx2), osterix, osteocalcin, collagen, type 1, alpha 1 (Col1A1) and osteonectin were detected to assess transcription factor-associated osteogenic differentiation. The mRNA and protein expression levels of osteoprotegerin (OPG) and receptor activator for nuclear factor-kappa B ligand (RANKL) were detected to assess cytokine-associated osteoclastogenesis. The results demonstrated that curcumin prevented the DXM-induced inhibition of the proliferative ability of the osteoblasts in a dose-dependent manner. In addition, curcumin upregulated the mRNA expression levels of transcription factors that favor osteoblast differentiation and increased the ratio of OPG to RANKL. Moreover, the effects of curcumin on the Wnt signaling pathway were also investigated. RT-qPCR and western blot analysis demonstrated that the Wnt signaling pathway, which was inhibited by DXM, was re-activated upon treatment with curcumin. Immunofluorescence staining revealed that curcumin restored the intranuclear staining of β-catenin in the DXM-stimulated osteoblasts. Collectively, our data demonstrate that curcumin may be a potential therapeutic agent for the treatment of GC-induced osteoporosis.