Department of Orthopedics, The First Affiliated Hospital of Nanchang University, Artificial Joints Engineering and Technology Research Center of Jiangxi Province, Nanchang, Jiangxi province, 330006, China; Multidisciplinary Therapy Center of Musculoskeletal Tumor, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi province, 330006, China.
Biochem Biophys Res Commun. 2019 Jan 15;508(3):902-906. doi: 10.1016/j.bbrc.2018.11.201. Epub 2018 Dec 8.
The receptor activator of nuclear factor-κB (NF-κB) ligand (RANKL)-RANK regulatory axis is a major regulator of osteoclast differentiation and activation. Icariin, a flavonol glycoside isolated from the Epimedium herb, has been reported to prevents bone loss in ovariectomized mice and inhibits wear particle-induced osteolysis. However, the molecular mechanism through which icariin inhibits RANKL-induced osteoclastogenesis has not been fully understood. Therefore, we aimed to investigate the effects of icariin on RANKL-induced osteoclastogenesis and to elucidate the mechanism underlying this effect. Our results showed that RANKL-induced osteoclastogenesis was inhibited by icariin in bone marrow macrophages (BMMs) and RAW264.7 cells, and that this effect was due to suppression of NF-κB and mitogen-activated protein kinase (MAPK) activation. In addition, icariin inhibited F-actin ring formation and attenuated the bone resorption ability of mature osteoclasts. Collectively, our results indicate that icariin may be a promising potential candidate for the treatment of osteolytic diseases such as osteoporosis. Moreover, our findings lay the foundation for understanding and intervening in osteoclast-related diseases at the molecular level.
核因子-κB（NF-κB）受体激活剂（RANKL）-RANK 调节轴是破骨细胞分化和激活的主要调节剂。淫羊藿素是从淫羊藿属植物中分离出来的一种黄酮醇糖苷，据报道可预防去卵巢小鼠的骨质流失，并抑制磨损颗粒诱导的骨溶解。然而，淫羊藿素抑制 RANKL 诱导的破骨细胞生成的分子机制尚未完全阐明。因此，我们旨在研究淫羊藿素对 RANKL 诱导的破骨细胞生成的影响，并阐明其作用机制。我们的结果表明，淫羊藿素可抑制骨髓巨噬细胞（BMM）和 RAW264.7 细胞中 RANKL 诱导的破骨细胞生成，这一作用是由于抑制 NF-κB 和丝裂原活化蛋白激酶（MAPK）的激活。此外，淫羊藿素抑制 F-肌动蛋白环的形成，并减弱成熟破骨细胞的骨吸收能力。总之，我们的研究结果表明淫羊藿素可能是治疗骨质疏松等溶骨性疾病的有前途的候选药物。此外，我们的研究结果为在分子水平上理解和干预破骨细胞相关疾病奠定了基础。
