<br>Orcinol gentiobioside 通过 JNK1 信号促进细胞凋亡和抑制自噬来抑制 RANKL 诱导的破骨细胞生成,Journal of Ethnopharmacology

当前位置： X-MOL 学术 › J. Ethnopharmacol. › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

Orcinol gentiobioside 通过 JNK1 信号促进细胞凋亡和抑制自噬来抑制 RANKL 诱导的破骨细胞生成
Journal of Ethnopharmacology ( IF 4.8 ) Pub Date : 2024-03-21 , DOI: 10.1016/j.jep.2024.118060
Chenxia Lian ₁ , Wan Gong ₂ , Xuan Zhao ₁ , Peng Sun ₁ , Sijing Hu ₁ , Guifen Zhou ₁ , Qiaoyan Zhang ₁ , Luping Qin ₁

Affiliation

骨质疏松症（OP）是一种代谢性疾病，其特征是破骨细胞骨吸收和成骨细胞骨形成破坏。 Gaertn 在中医和印度医学中用于治疗 OP 有着悠久的历史。 Orcinol gentiobioside (OGB) 是源自 Gaertn 的主要活性成分，已被证明具有抗 OP 活性。然而，OGB 调节破骨细胞骨吸收的治疗功效和机制仍不清楚。评价OGB对骨髓巨噬细胞（BMM）来源的破骨细胞形成、分化和功能的影响，进一步阐明OGB在OP中的作用机制。利用 BMM 衍生的破骨细胞来评估 OGB 对破骨细胞形成、分化和骨吸收的影响。进行抗酒石酸酸性磷酸酶（TRAP）染色和活性测定以指示破骨细胞的活性。通过 RT-PCR 和蛋白质印迹法测定破骨细胞相关基因和蛋白质。通过共聚焦激光显微镜观察F-肌动蛋白环的形成，通过倒置显微镜观察骨吸收凹坑。通过分子对接预测OGB在破骨细胞中的靶点，并通过细胞热位移分析（CETSA）和靶点激活剂的逆转作用进一步验证。通过流式细胞仪分析破骨细胞的凋亡情况，并通过共聚焦激光显微镜测定破骨细胞中的自噬通量。OGB抑制破骨细胞的形成和分化、破骨细胞相关基因和蛋白的表达、F-肌动蛋白环的形成和骨吸收活性。分子对接和CETSA分析表明OGB对c-Jun N端激酶1（JNK1）表现出良好的亲和力。此外，OGB诱导破骨细胞凋亡并抑制自噬，JNK激动剂茴香霉素逆转了OGB诱导的破骨细胞凋亡增加和自噬抑制。 OGB 通过 JNK1 信号传导促进细胞凋亡和减少自噬来抑制破骨细胞生成。

"点击查看英文标题和摘要"

Orcinol gentiobioside inhibits RANKL-induced osteoclastogenesis by promoting apoptosis and suppressing autophagy via the JNK1 signaling

Osteoporosis (OP) is a metabolic disorder characterized by disrupted osteoclastic bone resorption and osteoblastic bone formation. Gaertn has a long history of application in traditional Chinese and Indian medicine for treating OP. Orcinol gentiobioside (OGB) is a principal active constituent derived from Gaertn and has been shown to have anti-OP activity. However, the therapeutic efficacy and mechanism of OGB in modulating osteoclastic bone resorption remain undefined. To evaluate the effect of OGB on the formation, differentiation and function of osteoclasts derived from bone marrow macrophages (BMMs), and further elucidate the underlying action mechanism of OGB in OP. Osteoclasts derived from BMMs were utilized to evaluate the effect of OGB on osteoclast formation, differentiation and bone resorption. Tartrate-resistant acid phosphatase (TRAP) staining and activity assays were conducted to denote the activity of osteoclasts. Osteoclast-related genes and proteins were determined by RT-PCR and Western blotting assays. The formation of the F-actin ring was observed by confocal laser microscopy, and bone resorption pits were observed by inverted microscopy. The target of OGB in osteoclasts was predicted by using molecular docking and further verified by Cellular Thermal Shift Assay (CETSA) and reversal effects of the target activator. The apoptosis of osteoclasts was analyzed by flow cytometry, and autophagic flux in osteoclasts was determined by confocal laser microscopy OGB inhibited osteoclast formation and differentiation, osteoclast-related genes and proteins expression, F-actin ring formation, and bone resorption activity. Molecular docking and CETSA analysis demonstrated that OGB exhibited good affinity for c-Jun N-terminal Kinase 1 (JNK1). In addition, OGB induced apoptosis and inhibited autophagy in osteoclasts, and the JNK agonist anisomycin reversed the increase in apoptosis and inhibition of autophagy induced by OGB in osteoclasts. OGB inhibited osteoclastogenesis by promoting apoptosis and diminishing autophagy via JNK1 signaling.

更新日期：2024-03-21

点击分享查看原文

点击收藏

阅读更多本刊新发论文本刊介绍/投稿指南