Wang Xin, Zheng Ting, Kang Ju-Hee, Li Hua, Cho Hyewon, Jeon Raok, Ryu Jae-Ha, Yim Mijung
College of Pharmacy, Sookmyung Women's University, Cheongpa-ro 47-gil, Yongsan-gu, Seoul 04310, Republic of Korea.
College of Pharmacy, Sookmyung Women's University, Cheongpa-ro 47-gil, Yongsan-gu, Seoul 04310, Republic of Korea; Research Center for Cell Fate Control, Sookmyung Women's University, Cheongpa-ro 47-gil, Yongsan-gu, Seoul 04310, Republic of Korea.
Eur J Pharmacol. 2016 Mar 5;774:34-42. doi: 10.1016/j.ejphar.2016.01.008. Epub 2016 Jan 26.
Osteoclasts are the only cells capable of breaking down bone matrix, and excessive activation of osteoclasts is responsible for bone-destructive diseases. In this study, we investigated the effects of decursin from extract of Angelica gigas root on receptor activator of nuclear factor kappa B ligand (RANKL)-induced osteoclast formation using mouse bone marrow-derived macrophages (BMMs). Decursin inhibited RANKL-induced osteoclast formation without cytotoxicity. In particular, decursin maintains the characteristics of macrophages by blocking osteoclast differentiation by RANKL. Furthermore, the RANKL-stimulated bone resorption was diminished by decursin. Mechanistically, decursin blocked the RANKL-triggered ERK mitogen-activated protein kinases (MAPK) phosphorylation, which results in suppression of c-Fos and the nuclear factor of activated T cells (NFATc1) expression. In accordance with the in vitro study, decursin reduced lipopolysaccharide (LPS)- or ovariectomy (OVX)-induced bone loss in vivo. Therefore, decursin exerted an inhibitory effect on osteoclast formation and bone loss in vitro and in vivo. Decursin could be useful for the treatment of bone diseases associated with excessive bone resorption.
破骨细胞是唯一能够分解骨基质的细胞，破骨细胞的过度激活是导致骨破坏性疾病的原因。在本研究中，我们使用小鼠骨髓来源的巨噬细胞（BMMs）研究了当归根提取物中的紫花前胡素对核因子κB受体活化因子配体（RANKL）诱导的破骨细胞形成的影响。紫花前胡素抑制RANKL诱导的破骨细胞形成且无细胞毒性。特别是，紫花前胡素通过阻断RANKL诱导的破骨细胞分化来维持巨噬细胞的特性。此外，紫花前胡素减少了RANKL刺激的骨吸收。机制上，紫花前胡素阻断了RANKL触发的细胞外信号调节激酶丝裂原活化蛋白激酶（ERK MAPK）磷酸化，从而导致c-Fos和活化T细胞核因子（NFATc1）表达的抑制。与体外研究一致，紫花前胡素在体内减少了脂多糖（LPS）或卵巢切除（OVX）诱导的骨质流失。因此，紫花前胡素在体外和体内均对破骨细胞形成和骨质流失发挥抑制作用。紫花前胡素可能对治疗与过度骨吸收相关的骨疾病有用。
