Dendrobine attenuates osteoclast differentiation through modulating ROS/NFATc1/ MMP9 pathway and prevents inflammatory bone destruction,Phytomedicine

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Dendrobine attenuates osteoclast differentiation through modulating ROS/NFATc1/ MMP9 pathway and prevents inflammatory bone destruction
Phytomedicine ( IF 6.7 ) Pub Date : 2021-11-06 , DOI: 10.1016/j.phymed.2021.153838
Wende Deng ₁ , Zongbao Ding ₁ , Yiyuan Wang ₁ , Binhua Zou ₁ , Jiehuang Zheng ₁ , Yanhui Tan ₁ , Qin Yang ₁ , Minhong Ke ₁ , Yan Chen ₁ , Song Wang ₂ , Xiaojuan Li ₁

Affiliation

Background

: Osteolytic diseases share symptoms such as bone loss, fracture and pain, which are caused by over-activated osteoclasts. Targeting osteoclast differentiation has emerged as a therapeutic strategy clinically. Dendrobine is an alkaloid isolated from Chinese herb Dendrobium nobile, with knowing effects of analgesia and anti-inflammation. The roles of dendrobine on osteoclasts and osteolysis remain unclear.

Purpose

: Herein, the possible roles of dendrobine in osteoclastogenesis, inflammatory osteolysis and the underlying mechanism were explored.

Methods

: Bone marrow-derived macrophages (BMMs) and RAW264.7 cells were employed to evaluate the roles of dendrobine on osteoclastogenesis, bone absorption and the underlying mechanism in vitro. LPS injection was used to cause inflammatory osteolysis in vivo.

Results

: Dendrobine repressed osteoclastogenesis, bone resorption induced by receptor activator of nuclear factor kappa B ligand (RANKL) in vitro. Mechanistically, dendrobine inhibited RANKL-upregulated intracellular reactive oxygen species (ROS), p-p38, c-Fos expression and nuclear factor of activated T cells (NFATc1) nuclear translocation. Osteoclastic genes were reduced, and among them matrix metalloproteinase 9 (MMP9) mRNA was dramatically blocked by dendrobine. Moreover, it substantially suppressed MMP9 protein expression during osteoclastogenesis in vitro. Accordingly, oral 20 mg/kg/day dendrobine was capable of preventing LPS-induced osteolysis with decreased osteoclasts in vivo.

Conclusion

: Taken together, dendrobine suppresses osteoclastogenesis through restraining ROS, p38-c-Fos and NFATc1-MMP9 in vitro, thus attenuates inflammatory osteolysis in vivo. This finding supports the discover of dendrobine as a novel osteoclast inhibitor for impeding bone erosion in the future.

中文翻译：

石斛碱通过调节 ROS/NFATc1/MMP9 通路减弱破骨细胞分化并防止炎症性骨破坏

背景

：溶骨性疾病有共同的症状，如骨质流失、骨折和疼痛，这些症状都是由过度活化的破骨细胞引起的。靶向破骨细胞分化已成为临床治疗策略。石斛碱是从中草药石斛中分离得到的一种生物碱，具有镇痛和抗炎作用。石斛碱对破骨细胞和骨溶解的作用仍不清楚。

目的

: 本文探讨了石斛碱在破骨细胞生成、炎症性骨溶解中的可能作用及其潜在机制。

方法

: 使用骨髓来源的巨噬细胞 (BMM) 和 RAW264.7 细胞来评估石斛碱在体外对破骨细胞生成、骨吸收和潜在机制的作用。LPS注射用于引起体内炎症性骨溶解。

结果

: 石斛碱在体外抑制破骨细胞生成和由核因子 kappa B 配体 (RANKL) 受体激活剂诱导的骨吸收。从机制上讲，石斛碱抑制 RANKL 上调的细胞内活性氧 (ROS)、p-p38、c-Fos 表达和活化 T 细胞 (NFATc1) 核转位的核因子。破骨基因减少，其中基质金属蛋白酶 9 (MMP9) mRNA 被石斛碱显着阻断。此外，它在体外破骨细胞生成过程中显着抑制了 MMP9 蛋白的表达。因此，口服 20 mg/kg/天的石斛碱能够防止 LPS 诱导的骨溶解，同时体内破骨细胞减少。