Carnosol suppresses RANKL-induced osteoclastogenesis and attenuates titanium particles-induced osteolysis
Carnosol suppresses RANKL-induced osteoclastogenesis and attenuates titanium particles-induced osteolysis
复制标题
鼠尾草酚抑制 RANKL 诱导的破骨细胞生成并减弱钛颗粒诱导的骨溶解。
DOI：
10.1002/jcp.29978
复制
发表时间：
2020-07-28
影响因子：
5.6
通讯作者：
Zhang, Shuncong
中科院分区：
文献类型：
--
作者：
Li, Yongxian;Lin, Sipeng;Zhang, Shuncong
骨质溶解是一种常见的医学病症，其特征在于破骨细胞的过度活性和骨吸收，导致严重的生活质量差。因此，寻找能有效抑制破骨细胞过度分化和功能的药物，以预防和减少溶骨性疾病的发生是非常必要的。据报道，从迷迭香和迷迭香中分离的鼠尾草酚（Carnosol，Car）具有抗炎、抗氧化和抗癌作用，但其对骨质溶解的活性尚未确定。在这项研究中，我们发现Car对核因子-κ B配体受体激活剂（RANKL）诱导的破骨细胞分化具有强烈的抑制作用，且呈剂量依赖性，没有任何可观察到的细胞毒性。Car通过影响MAPK、NF-κ B B和Ca 2+信号通路，抑制NFATc 1，从而抑制RANKL诱导的破骨细胞生成和骨吸收功能。此外，颗粒诱导的骨溶解小鼠模型证实了Car可以有效地治疗体内骨丢失。因此，Car通过抑制RANKL诱导的破骨细胞的形成和功能，可能成为预防或治疗骨质溶解的一种治疗补充剂。
Osteolysis is a common medical condition characterized by excessive activity of osteoclasts and bone resorption, leading to severe poor quality of life. It is essential to identify the medications that can effectively suppress the excessive differentiation and function of osteoclasts to prevent and reduce the osteolytic conditions. It has been reported that Carnosol (Car), isolated from rosemary and salvia, has anti-inflammatory, antioxidative, and anticancer effects, but its activity on osteolysis has not been determined. In this study, we found that Car has a strong inhibitory effect on the receptor activator of nuclear factor-kappa B ligand (RANKL)-induced osteoclast differentiation dose-dependently without any observable cytotoxicity. Moreover, Car can inhibit the RANKL-induced osteoclastogenesis and resorptive function via suppressing NFATc1, which is a result of affecting MAPK, NF-kappa B and Ca2+ signaling pathways. Moreover, the particle-induced osteolysis mouse model confirmed that Car could be effective for the treatment of bone loss in vivo. Taken together, by suppressing the formation and function of RANKL-induced osteoclast, Car, may be a therapeutic supplementary in the prevention or the treatment of osteolysis.