Sciadopitysin suppresses RANKL-mediated osteoclastogenesis and prevents bone loss in LPS-treated mice
Sciadopitysin suppresses RANKL-mediated osteoclastogenesis and prevents bone loss in LPS-treated mice
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Sciadopitysin 抑制 RANKL 介导的破骨细胞生成并防止 LPS 处理的小鼠骨质流失
DOI：
10.1016/j.intimp.2017.05.029
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发表时间：
2017-08-01
影响因子：
5.6
通讯作者：
Sun, Wan-chun
中科院分区：
文献类型：
--
作者：
Cao, Jinjin;Lu, Qiang;Sun, Wan-chun
scidopitysin（Sc）是一种双黄酮类化合物，可保护活性氧（ROS）介导的成骨细胞功能障碍，但其在破骨细胞发生中的作用尚不清楚。在这项研究中，我们观察到Sc剂量依赖性地抑制RANKL诱导的破骨细胞生成和骨吸收。我们的研究结果表明，Sc处理强烈降低RANKL诱导的成骨细胞特异性基因表达，包括组织蛋白酶K（CTSK），抗酒石酸酸性磷酸酶（TRAP）和MMP-9。此外，Sc明显减弱RANKL增加的c-Fos和NFATc 1表达。同时，Sc还显著抑制NF-κ B B的活化，而不改变MAPK（p38、JNK和ERK 1/2）的磷酸化。最后，我们的研究表明，Sc给药可以逆转LPS诱导的小鼠模型的骨丢失。这项研究表明，Sc通过抑制NF-κ B活化和减少c-Fos和NFATc 1的表达来抑制RANKL诱导的破骨细胞生成和骨丢失。因此，Sc可能对RANKL介导的溶骨性骨疾病有益。
Previous studies reported that sciadopitysin (Sc), a type of biflavonoids, protects reactive oxygen species (ROS) mediated osteoblast dysfunction, but its role in osteoclastogenesis remains unclear. In this study, we observed that Sc dose-dependently suppressed RANKL-induced osteoclastogenesis and bone resorption. Our results indicated that Sc treatment strongly reduced RANKL-induced osteodast-specific genes expression, including cathepsin K (CTSK), tartrate-resistant acid phosphatase (TRAP) and MMP-9. Furthermore, Sc apparently attenuated RANKL-increased expressions of c-Fos and NFATc1. Meanwhile, Sc also strikingly inhibited the activation of NF-kappa B without altering the phosphorylation of MAPKs (p38, JNK and ERK1/2). Finally, our study demonstrated that Sc administration could reverse the bone loss in LPS-induced mice model. This study suggests that Sc inhibits RANKL-induced osteoclastogenesis and bone loss by inhibiting NF-kappa B activation and reducing the expression of c-Fos and NFATc1. Therefore, Sc might be benefit for RANKL-mediated osteolytic bone diseases.