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Nrf2通过用AM630使2型大麻素受体失活来抑制破骨细胞RANKL诱导的RAW 264.7细胞分化。

Nrf2 is required for suppressing osteoclast RANKL-induced differentiation in RAW 264.7 cells via inactivating cannabinoid receptor type 2 with AM630.

作者信息

Li Wan, Sun Yongxin

机构信息

Geriatric Cardiovascular Department, The First Hospital Affiliated to China Medical University, Shenyang, Liaoning, China.

Department of Rehabilitation, The First Hospital Affiliated to China Medical University, Shenyang, Liaoning, China.

出版信息

Regen Ther. 2020 Mar 2;14:191-195. doi: 10.1016/j.reth.2020.02.001. eCollection 2020 Jun.

DOI:10.1016/j.reth.2020.02.001
PMID:32154333
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7056625/
Abstract

OBJECTIVE

Nuclear factor-erythroid 2-related factor 2 (Nrf2) is shown to as a negative-regulatory cause in osteoclasts differentiation. Cannabinoid receptor type 2 (CB2) is verified to regulate osteoclast differentiation, though with diversed results.

METHODS

In current research, we studied the Nrf2 role on osteoclast differentiation regulation with the CB2-selective agonists, AM1241, or CB2-selective antagonist, AM630, in RAW 264.7 macrophages. The nuclear factor-κB ligand (RANKL)-induced osteoclast differentiation activator was confirmed by tartrate-resistant acid phosphatase (TRAP) staining as well as the TRAP activity analysis. In addition, Nrf2 siRNA was used to characterize the function of Nrf2 during osteoclast differentiation. We analyzed HO-1 and Nrf2 proteins levels with western blotting.

RESULTS

The results showed that AM1241 promoted, while AM630 suppressed, osteoclast differentiation in RAW 264.7 cells. Both AM1241 and AM630 increased the expressions of HO-1 and Nrf2. Nrf2 silencing promoted osteoclast differentiation and abolished the function of AM630 to inhibit osteoclast differentiation.

CONCLUSIONS

Our results suggested that Nrf2 was required for inhibiting osteoclast differentiation induced by RANKL of RAW 264.7 cells by AM630, which may provide the insights of a novel method to treat osteoclastogenic bone disease.

摘要

目的

核因子红系2相关因子2(Nrf2)被证明是破骨细胞分化的负调控因子。2型大麻素受体(CB2)已被证实可调节破骨细胞分化,不过结果存在差异。

方法

在本研究中,我们使用CB2选择性激动剂AM1241或CB2选择性拮抗剂AM630,在RAW 264.7巨噬细胞中研究Nrf2在破骨细胞分化调节中的作用。通过抗酒石酸酸性磷酸酶(TRAP)染色以及TRAP活性分析,确认核因子κB受体活化因子配体(RANKL)诱导的破骨细胞分化激活剂。此外,使用Nrf2 siRNA来表征Nrf2在破骨细胞分化过程中的功能。我们通过蛋白质印迹分析HO-1和Nrf2蛋白水平。

结果

结果表明,AM1241促进RAW 264.7细胞中的破骨细胞分化,而AM630抑制该分化。AM1241和AM630均增加HO-1和Nrf2的表达。Nrf2沉默促进破骨细胞分化,并消除AM630抑制破骨细胞分化的功能。

结论

我们的结果表明,Nrf2是AM630抑制RAW 264.7细胞中RANKL诱导的破骨细胞分化所必需的,这可能为治疗破骨性骨疾病的新方法提供思路。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6ae9/7056625/8f773e4294ff/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6ae9/7056625/525166769756/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6ae9/7056625/b9b3f9fca887/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6ae9/7056625/8f773e4294ff/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6ae9/7056625/525166769756/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6ae9/7056625/b9b3f9fca887/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6ae9/7056625/8f773e4294ff/gr3.jpg

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