<br>Dauricine 通过抑制 ROS 介导的 NF-κB 和 NFATc1 活性来减轻卵巢切除引起的骨质流失和 RANKL 诱导的破骨细胞生成,Phytomedicine

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Dauricine 通过抑制 ROS 介导的 NF-κB 和 NFATc1 活性来减轻卵巢切除引起的骨质流失和 RANKL 诱导的破骨细胞生成
Phytomedicine ( IF 6.7 ) Pub Date : 2024-03-20 , DOI: 10.1016/j.phymed.2024.155559
Xixi Lin ₁ , Guixin Yuan ₂ , Bin Yang ₃ , Chunlan Xie ₄ , Zhigao Zhou ₅ , Ying Liu ₁ , Zhijuan Liu ₆ , Zuoxing Wu ₁ , Yoshie Akimoto ₇ , Na Li ₁ , Ren Xu ₈ , Fangming Song ₉

Affiliation

The First Affiliated Hospital of Xiamen University-ICMRS Collaborating Center for Skeletal Stem Cells, State Key Laboratory of Cellular Stress Biology, School of Medicine, Xiamen University, Xiamen, Fujian, 361100, China; Xiamen Key Laboratory of Regeneration Medicine, Fujian Provincial Key Laboratory of Organ and Tissue Regeneration, School of Medicine, Xiamen University, Xiamen, 361100, China.
The First Affiliated Hospital of Xiamen University-ICMRS Collaborating Center for Skeletal Stem Cells, State Key Laboratory of Cellular Stress Biology, School of Medicine, Xiamen University, Xiamen, Fujian, 361100, China; Xiamen Key Laboratory of Regeneration Medicine, Fujian Provincial Key Laboratory of Organ and Tissue Regeneration, School of Medicine, Xiamen University, Xiamen, 361100, China; Department of Orthopedics, The Second Affiliated Hospital of Shantou University Medical College, Shantou University Medical College, Shantou, Guangdong, 515044, China.
Department of Anesthesiology, The First Affiliated Hospital of Xiamen University, Xiamen, Fujian, 361000, China.
The First Affiliated Hospital of Xiamen University-ICMRS Collaborating Center for Skeletal Stem Cells, State Key Laboratory of Cellular Stress Biology, School of Medicine, Xiamen University, Xiamen, Fujian, 361100, China.
Department of Orthopedics, The Second Affiliated Hospital of Shantou University Medical College, Shantou University Medical College, Shantou, Guangdong, 515044, China.
Life Sciences Institute, Guangxi Medical University, Nanning, Guangxi, 530021, China; Collaborative Innovation Centre of Regenerative Medicine and Medical Bio Resource Development and Application Co-constructed by the Province and Ministry, Guangxi Medical University, Nanning, Guangxi, 530021, China.
Iskra Industry Co., Ltd., Tokyo 103-0027, Japan.
The First Affiliated Hospital of Xiamen University-ICMRS Collaborating Center for Skeletal Stem Cells, State Key Laboratory of Cellular Stress Biology, School of Medicine, Xiamen University, Xiamen, Fujian, 361100, China; Xiamen Key Laboratory of Regeneration Medicine, Fujian Provincial Key Laboratory of Organ and Tissue Regeneration, School of Medicine, Xiamen University, Xiamen, 361100, China; Collaborative Innovation Centre of Regenerative Medicine and Medical Bio Resource Development and Application Co-constructed by the Province and Ministry, Guangxi Medical University, Nanning, Guangxi, 530021, China.
Xiamen Key Laboratory of Regeneration Medicine, Fujian Provincial Key Laboratory of Organ and Tissue Regeneration, School of Medicine, Xiamen University, Xiamen, 361100, China; Life Sciences Institute, Guangxi Medical University, Nanning, Guangxi, 530021, China; Collaborative Innovation Centre of Regenerative Medicine and Medical Bio Resource Development and Application Co-constructed by the Province and Ministry, Guangxi Medical University, Nanning, Guangxi, 530021, China.

破骨细胞在维持骨合成代谢和骨分解代谢之间的平衡中起着重要作用。破骨细胞的异常与骨质疏松、类风湿性关节炎、肿瘤骨转移等溶骨性骨疾病密切相关。我们的目标是寻找可以抑制破骨细胞形成和功能的天然化合物。在这项研究中，我们评估了 Dauricine (Dau) 对破骨细胞形成和功能的影响，及其在卵巢切除小鼠模型中预防骨质流失的潜力。进行了多项实验，包括破骨细胞生成、足体带形成、骨吸收测定、RNA测序、实时定量PCR、ROS水平检测、表面等离子体共振测定、荧光素酶测定和蛋白质印迹。为了验证效果，构建了卵巢切除小鼠模型（OVX模型），并使用显微CT和组织学测量了骨参数。此外，对 OVX 模型的血清样本进行了代谢组学分析。实验表明，Dau 抑制 RANKL 诱导的破骨细胞生成、足体带形成和骨吸收功能。 RNA 测序结果显示，Dau 显着抑制与破骨细胞相关的基因。功能富集分析表明Dau对破骨细胞的抑制作用可能与NF-κB信号通路和活性氧代谢通路有关。分子对接、表面等离子共振测定和蛋白质印迹分析进一步表明，Dau 通过调节 ROS/NF-κB/NFATc1 通路抑制 RANKL 诱导的破骨细胞生成。此外，对 OVX 诱导的小鼠施用 Dau 验证了其治疗骨质流失疾病的功效。 Dau 通过抑制破骨细胞活性和骨吸收来防止 OVX 引起的骨质流失，这可能为预防和治疗骨质疏松症等代谢性骨疾病提供新方法。这项研究为 Dau 在 OVX 模型中的抑制作用提供了创新的见解，并阐明了潜在的机制。

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Dauricine attenuates ovariectomized-induced bone loss and RANKL-induced osteoclastogenesis via inhibiting ROS-mediated NF-κB and NFATc1 activity

Osteoclast plays an important role in maintaining the balance between bone anabolism and bone catabolism. The abnormality of osteoclast is closely related to osteolytic bone diseases such as osteoporosis, rheumatoid arthritis and tumor bone metastasis. We aim to search for natural compound that may suppress osteoclast formation and function. In this study, we assessed the impact of Dauricine (Dau) on the formation and function of osteoclasts , as well as its potential in preventing bone loss in an ovariectomy mouse model . Multiple experiments were carried out, including osteoclastogenesis, podosomal belt formation, bone resorption assay, RNA-sequencing, real-time quantitative PCR, ROS level detection, surface plasmon resonance assay, luciferase assay and western blot. To verify the effect , an ovariectomized mouse model (OVX model) was constructed, and bone parameters were measured using micro-CT and histology. Furthermore, metabolomics analysis was performed on blood serum samples from the OVX model. experiments demonstrated that Dau inhibits RANKL-induced osteoclastogenesis, podosomal belt formation, and bone resorption function. RNA-sequencing results revealed that Dau significantly suppresses genes related to osteoclast. Functional enrichment analysis indicated that Dau's inhibition of osteoclasts may be associated with NF-κB signaling pathway and reactive oxygen metabolism pathway. Molecular docking, surface plasmon resonance assay and western blot analysis further ed that Dau inhibits RANKL-induced osteoclastogenesis by modulating the ROS/NF-κB/NFATc1 pathway. Moreover, administration of Dau to OVX-induced mice validated its efficacy in treating bone loss disease. Dau prevents OVX-induced bone loss by inhibiting osteoclast activity and bone resorption, potentially offering a new approach for preventing and treating metabolic bone diseases such as osteoporosis. This study provides innovative insights into the inhibitory effects of Dau in an OVX model and elucidates the underlying mechanism.

更新日期：2024-03-20

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