Ligustilide suppresses RANKL‐induced osteoclastogenesis and bone resorption via inhibition of RANK expression

Ligustilide suppresses RANKL‐induced osteoclastogenesis and bone resorption via inhibition of RANK expression
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藁本内酯通过抑制 RANK 表达来抑制 RANKL 诱导的破骨细胞生成和骨吸收

DOI:
10.1002/jcb.29153
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发表时间:
2019-08
影响因子:
4
通讯作者:
Guoping Zhao
Guoping Zhao
中科院分区:
生物学2区
文献类型:
--
作者:
Dairong Wang;Jia Li;Wenyu Feng;Jun Yao;Luanhai Ou;Shijie Liao;Yun Liu;Boxiang Li;Chengsen Lin;Jinmin Zhao;Guoping Zhao

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破骨细胞(OC)是唯一参与骨吸收的细胞。OC的功能障碍会导致各种骨疾病。当归内酯(LIG)是当归挥发油的主要成分。LIG具有多种药理活性,但其对破骨细胞生成和骨吸收的影响尚不清楚。我们的研究表明,LIG以剂量依赖性方式抑制核因子-κB受体激活剂(NF-κB)配体诱导的OC形成和活化。此外,LIG下调OC特异性基因的信使RNA(mRNA)表达,如V-ATP酶d2、抗酒石酸酸性磷酸酶、树突状细胞特异性跨膜蛋白、组织蛋白酶K和活化T细胞cl的核因子。此外,LIG阻断了NF-κB/细胞外信号调节激酶/p38/免疫受体酪氨酸基序激活信号通路的激活。重要的是,LIG抑制了肿瘤坏死因子受体相关因子6蛋白的表达和NF-κB mRNA受体激活剂的表达。但是,LIG并不影响成骨细胞的形成和矿化。总的来说,这一观察结果表明,LIG可作为一种有前途的药物,用于预防和治疗由异常骨吸收引起的疾病。
Osteoclast (OC) is the only cell involved in bone resorption. Dysfunction of OCs leads to a variety of bone diseases. Ligustilide (LIG) is the main component of the volatile oil isolated and purified from Angelica sinensis. LIG exerts many pharmacological activities, but its effects on osteoclastogenesis and bone resorption are still unclear. Our study showed that LIG inhibited receptor activator of nuclear factor‐κB (NF‐κB) ligand‐induced OC formation and activation in a dose‐dependent manner. Additionally, LIG downregulated the messenger RNA (mRNA) expression of OC‐specific genes, such as V‐ATPase d2, tartrate‐resistant acid phosphatase, a dendritic cell‐specific transmembrane protein, cathepsin K, and nuclear factor of activated T cells cl. Furthermore, LIG blocked the activation of NF‐κB/extracellular signal‐regulated kinase/p38/immunoreceptor tyrosine‐based activation motif signaling pathways. Crucially, the expression of tumor necrosis factor receptor‐associated factor 6 proteins and the expression of receptor activator of NF‐κB mRNA were inhibited by LIG. However, LIG did not affect the formation and mineralization of osteoblasts. Collectively, this observation suggests that LIG may serve as a promising agent for the prevention and treatment of diseases caused by abnormal bone resorption.
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