Notopterol Attenuates Estrogen Deficiency-Induced Osteoporosis via Repressing RANKL Signaling and Reactive Oxygen Species.
Notopterol Attenuates Estrogen Deficiency-Induced Osteoporosis via Repressing RANKL Signaling and Reactive Oxygen Species.
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Notopterol 通过抑制 RANKL 信号传导和活性氧来减轻雌激素缺乏引起的骨质疏松症
DOI：
10.3389/fphar.2021.664836
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发表时间：
2021
影响因子：
5.6
通讯作者：
Chen P
中科院分区：
文献类型：
--
作者：
Chen D;Wang Q;Li Y;Sun P;Kuek V;Yuan J;Yang J;Wen L;Wang H;Xu J;Chen P
骨骼的完整性通过骨重建单位中破骨细胞和成骨细胞的平衡活动得以维持。这种平衡可能会因破骨细胞过度活化而被打破，这在骨质疏松症中很常见。羌活醇（NOT）是羌活的主要成分，在生物医学药理学方面具有广泛作用。在我们的研究中，通过酒石酸抗性酸性磷酸酶（TRAcP）染色和羟基磷灰石吸收试验，我们发现NOT作为一种抑制剂，可调节RANKL激活的破骨细胞形成和骨吸收功能。此外，NOT阻碍了包括丝裂原活化蛋白激酶（MAPK）、核因子κB（NF-κB）和钙骨化在内的RANKL介导的信号通路，而促进了Nrf2/Keap1/ARE信号通路中的活性氧（ROS）清除酶。另外，NOT几乎完全抑制了RANKL介导的破骨细胞生成过程中关键转录因子NFATc1的激活。更重要的是，通过骨组织形态计量学、TRAcP染色和苏木精 - 伊红（H&E）染色测定，NOT通过阻断破骨细胞生成，减少了去卵巢（OVX）小鼠临床前模型中的骨量流失。总之，我们的研究结果表明，在体外，NOT可通过减弱RANKL介导的MAPK、NF-κB、钙和NFATc1信号转导通路以及增强Nrf2/Keap1/ARE通路中的ROS清除酶，来阻止破骨细胞生成和骨吸收活性；在体内，可抑制OVX诱导的骨丢失。综上所述，NOT可能被确定为一种天然的新型溶骨性疾病治疗药物。
Integrity of the skeleton is sustained through the balanced activities of osteoblasts and osteoclasts in bone remodeling unit. The balance can be disrupted by excessive osteoclasts activation commonly seen in osteoporosis. Notopterol (NOT) is a main component of Notopterygium incisum which exerts a wide spectrum effect on biomedical pharmacology. In our study, we found NOT serves as an inhibitor in regulating RANKL-activated osteoclasts formation and bone resorption function by calculating tartrate resistant acid phosphatase (TRAcP) staining and hydroxyapatite resorption assays. Furthermore, RANKL-mediated signaling pathways including MAPK, NF-κB and calcium ossification were hampered, whereas ROS scavenging enzymes in Nrf2/Keap1/ARE signaling pathways were promoted by NOT. In addition, the activation of the essential transcription factor NFATc1 in RANKL-mediated osteoclastogenesis was almost totally suppressed by NOT. What is more, NOT diminished the loss of bone mass in preclinical model of OVX mice by blocking osteoclastogenesis determined by bone histomorphometry, TRAcP staining and H&E staining. Conclusively, our findings demonstrated that NOT could arrest osteoclastogenesis and bone resorptive activity by attenuating RANKL-mediated MAPK, NF-κB, calcium and NFATc1 signaling transduction pathways and enhancing ROS scavenging enzymes in Nrf2/Keap1/ARE pathways in vitro, and prohibit bone loss induced by OVX in vivo. Taken together, NOT may be identified to be a natural and novel treatment for osteolytic diseases.
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DOI：
10.1074/jbc.m113.478545
发表时间：
2013-08-09
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Kanzaki H;Shinohara F;Kajiya M;Kodama T
通讯作者：
Kodama T
影响因子：
4.8
作者：
Kim, Min Seuk;Yang, Yu-Mi;Shin, Dong Min
通讯作者：
Shin, Dong Min
DOI：
10.1196/annals.1365.035
发表时间：
2006-01-01
期刊：
WOMEN'S HEALTH AND DISEASE: GYNECOLOGIC, ENDOCRINE, AND REPRODUCTIVE ISSUES
影响因子：
--
作者：
Hadjidakis, Dimitrios J.;Androulakis, Ioannis I.
通讯作者：
Androulakis, Ioannis I.
影响因子：
64.8
作者：
Chang, LF;Karin, M
通讯作者：
Karin, M
DOI：
10.1073/pnas.85.18.6706
发表时间：
1988-09-01
影响因子：
11.1
作者：
LADNER, MB;MARTIN, GA;STANLEY, ER
通讯作者：
STANLEY, ER