Department of Dental Pharmacology, School of Dentistry and Institute of Oral Bioscience, Brain Korea 21 project, Chonbuk National University, Jeonju 561-756, Republic of Korea.
Eur J Pharmacol. 2013 Sep 5;715(1-3):96-104. doi: 10.1016/j.ejphar.2013.06.002. Epub 2013 Jun 19.
Hispidulin, a flavonoid that is known to have anti-inflammatory and anti-oxidant effects, attenuates osteoclastogenesis and bone resorption. To investigate the molecular mechanism of its inhibitory effect on osteoclastogenesis, we employed the receptor activator of the nuclear factor κB (NF-κB) ligand (RANKL)-induced murine monocyte/macrophage RAW 264.7 cells and bone marrow-derived macrophages (BMMs) for osteoclastic differentiation in vitro. The inhibitory effect on in vitro osteoclastogenesis was evaluated by counting the number of tartrate-resistant acid phosphatase (TRAP)-positive multinucleated cells and by measuring the expression levels of osteoclast-specific genes such as matrix metalloproteinase 9 (MMP9), TRAP and cathepsin K. Similarly, hispidulin significantly inhibited osteoclast activity in RAW 264.7 cell as well as stimulated the ALP activity of MC3T3E1 cells. Furthermore, the in vivo suppressive effect on bone loss was assessed quantitatively in a lipopolysaccharide (LPS)-induced mouse model using microcomputational tomography (μCT) and histochemical analyses. Hispidulin was found to inhibit RANKL-induced activation of Jun N-terminal kinase (JNK) and p38, in addition to NF-κB in vitro experiment. Additionally, hispidulin decreased NFATc1 transcriptional activity in RANKL-induced osteoclastogenesis. This study identifies hispidulin as a potent inhibitor of osteoclastogenesis and bone resorption and provides evidence for its therapeutic potential to treat diseases involving abnormal bone lysis.
山金车二醇是一种具有抗炎和抗氧化作用的类黄酮，可减弱破骨细胞的生成和骨质吸收。为了研究其抑制破骨细胞生成的分子机制，我们采用核因子κB（NF-κB）受体激活配体（RANKL）诱导的鼠单核/巨噬细胞 RAW 264.7 细胞和骨髓来源的巨噬细胞（BMM）在体外进行破骨细胞分化。通过抗酒石酸酸性磷酸酶（TRAP）阳性多核细胞计数和测量破骨细胞特异性基因如基质金属蛋白酶 9（MMP9）、TRAP 和组织蛋白酶 K 的表达水平来评估对体外破骨细胞生成的抑制作用。同样，山金车二醇显著抑制 RAW 264.7 细胞中的破骨细胞活性，并刺激 MC3T3E1 细胞的碱性磷酸酶（ALP）活性。此外，通过微计算机断层扫描（μCT）和组织化学分析，在脂多糖（LPS）诱导的小鼠模型中定量评估其对骨丢失的抑制作用。山金车二醇被发现可抑制 RANKL 诱导的 Jun N-末端激酶（JNK）和 p38 的激活，以及体外实验中的 NF-κB。此外，山金车二醇降低了 RANKL 诱导的破骨细胞生成中的 NFATc1 转录活性。本研究将山金车二醇鉴定为一种有效的破骨细胞生成和骨质吸收抑制剂，并为其治疗涉及异常骨溶解的疾病提供了治疗潜力的证据。
