Naringin regulates bone metabolism in glucocorticoid-induced osteonecrosis of the femoral head via the Akt/Bad signal cascades
Naringin regulates bone metabolism in glucocorticoid-induced osteonecrosis of the femoral head via the Akt/Bad signal cascades
复制标题
柚皮苷通过 Akt/Bad 信号级联调节糖皮质激素诱导的股骨头坏死中的骨代谢
DOI：
10.1016/j.cbi.2019.03.008
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发表时间：
2019-05-01
影响因子：
5.1
通讯作者：
Ma, Xin-long
中科院分区：
文献类型：
--
作者：
Kuang, Ming-jie;Zhang, Wei-hao;Ma, Xin-long
目的：糖皮质激素性股骨头坏死（GIONFH）是长期或大剂量使用糖皮质激素后的常见疾病。GIONFH的发病机制仍存在争议，糖皮质激素（GCs）引起的骨代谢异常可能是重要因素之一。由于其对骨重建的积极作用，柚皮苷在骨代谢相关疾病中显示出潜在的治疗作用。在这项研究中，我们假设，柚苷调节骨代谢在大鼠GIONFH通过Akt/Bad信号cascades.Methods：在体外，地塞米松（Dex）或柚苷处理的细胞模型被用来评估柚苷的功能。在体内，采用甲基强的松龙（MPS）治疗的大鼠模型来评价柚皮苷在GONFH中的作用。体外实验采用CCK-8和Edu染色检测骨细胞增殖情况，TUNEL法、Annexin V-FITC-PI和Western blotting检测骨细胞凋亡情况。我们还验证了柚皮苷对成骨和破骨细胞生成的影响。在体内，我们使用显微CT（计算机断层扫描），组织学和免疫组化分析，以评估柚皮苷的影响。结果：体外实验结果表明，柚皮苷激活Akt后可促进成骨细胞的增殖，激活Akt后可抑制破骨细胞的增殖，激活Akt后可抑制破骨细胞的生成，抑制破骨细胞的凋亡。根据体内研究，柚皮苷防止GIONFH大鼠模型所示的micro-CT扫描和组织学和免疫组化analysis.Conclusions：因此，我们得出结论，柚皮苷是一种有效的化合物，促进骨修复和防止骨丢失的大鼠GIONFH通过Akt/Bad信号级联。
Purpose: Glucocorticoid-induced osteonecrosis of the femoral head (GIONFH) is a common disease following long-term use or large doses of glucocorticoids. The pathogenesis of GIONFH remains controversial, and abnormal bone metabolism caused by glucocorticoids(GCs) may be one of the important factors. Due to its positive effect on bone remodeling, naringin shows potential therapeutic effects in bone metabolism-related diseases. In this study, we hypothesized that naringin regulated bone metabolism in rat GIONFH via the Akt/Bad signal cascades.Methods: In vitro, a dexamethasone (Dex)- or naringin-treated cell model was used to evaluate the function of naringin. In vivo, methylprednisolone (MPS)-treated rat model was used to evaluate the function of naringin in GIONFH. In vitro, Cell Counting Kit-8 (CCK-8) and Edu staining was used to evaluate the proliferation of osteocytes, and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay, Annexin V-FITC-PI, and western blotting were used to evaluate the apoptosis of osteocytes. We also verified the effects of naringin on osteogenesis and osteoclastogenesis. In vivo, we used micro-CT (computed tomography), histological, and immunohistochemical analysis to evaluate the effect of naringin. Moreover, the mechanism of naringin regulating the bone metabolism through the Akt/Bad pathway was also investigated using bioinformatics analysis and western blotting.Results: The results of in vitro study showed that Akt activated by naringin promoted osteogenesis and osteocyte proliferation; in addition, osteocyte apoptosis and osteoclastogenesis was inhibited by Akt activation and Bad suppression. According to the in vivo study, naringin prevented GIONFH in a rat model as shown by micro-CT scanning and histological and immunohistochemical analysis.Conclusions: Therefore, we concluded that naringin is an effective compound for promoting bone repair and preventing bone loss in rats with GIONFH through Akt/Bad signal cascades.