Department of Dental Pharmacology, School of Dentistry and Institute of Oral Bioscience, Brain Korea 21 project, Chonbuk National University, Jeon-Ju 561-756, Republic of Korea.
Eur J Pharmacol. 2010 Jun 25;636(1-3):28-35. doi: 10.1016/j.ejphar.2010.03.023. Epub 2010 Mar 29.
Osteoclasts are specialized bone-resorbing cells derived from multipotent myeloid progenitor cells. They play a crucial homeostatic role in skeletal modeling and remodeling and destroy bone in many pathologic conditions. Receptor activator of NF-kappaB ligand (RANKL) is essential to osteoclastogenesis. In this study, we investigated the effects of Ikarisoside A, isolated from Epimedium koreanum (Berberidaceae), on osteoclastogenesis in RANKL-treated murine monocyte/macrophage RAW 264.7 cells. The results indicate that Ikarisoside A is a potent inhibitor of osteoclastogenesis in RANKL-stimulated RAW 264.7 cells as well as in bone marrow-derived macrophages. The inhibitory effect of Ikarisoside A resulted in decrease of osteoclast-specific genes like matrix metalloproteinase 9 (MMP9), tartrate-resistant acid phosphatase (TRAP), receptor activator of NF-kappaB (RANK), and cathepsin K. Moreover, Ikarisoside A blocked the resorbing capacity of RAW 264.7 cells on calcium phosphate-coated plates. Ikarisoside A also has inhibitory effects on the RANKL-mediated activation of NF-kappaB, JNK, and Akt. Finally, Ikarisoside A clearly decreased the expression of c-Fos and nuclear factor of activated T cells c1 (NFATc1) as well as the transcriptional activity of NFATc1, the master regulator of osteoclast differentiation. The data indicate that Ikarisoside A has potential for use in treatment of diseases involving abnormal bone lysis such as osteoporosis, rheumatoid arthritis, and periodontal bone erosion.
破骨细胞是一种来源于多能髓系前体细胞的专门的骨吸收细胞。它们在骨骼建模和重塑中起着至关重要的动态平衡作用，并在许多病理条件下破坏骨骼。核因子-κB 配体（RANKL）受体激活剂对破骨细胞生成至关重要。在这项研究中，我们研究了从淫羊藿（小檗科）中分离出的淫羊藿苷 A 对 RANKL 处理的鼠单核/巨噬细胞 RAW 264.7 细胞中破骨细胞生成的影响。结果表明，淫羊藿苷 A 是 RANKL 刺激的 RAW 264.7 细胞以及骨髓来源的巨噬细胞中破骨细胞生成的有效抑制剂。淫羊藿苷 A 的抑制作用导致破骨细胞特异性基因如基质金属蛋白酶 9（MMP9）、抗酒石酸酸性磷酸酶（TRAP）、核因子-κB 受体激活剂（RANK）和组织蛋白酶 K 的减少。此外，淫羊藿苷 A 阻断了 RAW 264.7 细胞在磷酸钙涂层板上的吸收能力。淫羊藿苷 A 还对 RANKL 介导的 NF-κB、JNK 和 Akt 的激活具有抑制作用。最后，淫羊藿苷 A 明显降低了 c-Fos 和激活 T 细胞核因子 c1（NFATc1）的表达以及 NFATc1 的转录活性，NFATc1 是破骨细胞分化的主要调节因子。数据表明，淫羊藿苷 A 具有用于治疗涉及异常骨溶解的疾病的潜力，如骨质疏松症、类风湿性关节炎和牙周骨侵蚀。
