Cong Fei, Liu Jian, Wang Chunmei, Yuan Zhi, Bi Long, Liang Jidong, Su Ke, Qiu Yucheng, Song Tao, Fan Jinzhu, Chao Gao
Institute of Orthopedic Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China; Department of Orthopaedics, Honghui Hospital, Xi'an Jiaotong University, Xi'an 710054, China.
Institute of Orthopedic Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China.
Biomed Pharmacother. 2017 Aug;92:927-934. doi: 10.1016/j.biopha.2017.05.115. Epub 2017 Jun 8.
Ginsenoside-Rb2 (Rb2) is a 20(S)-protopanaxadiol glycoside extracted from ginseng possessing various bioactivities which has drawn considerable interest regarding the area of bone metabolism. However, the effect of Rb2 on osteoclast differentiation remains unknown. In this study, we aimed to investigate the potential role of Rb2 in regulating osteoclast differentiation and the underlying molecular mechanisms. Osteoclast differentiation was induced by receptor activator nuclear factor-kappaB (NF-κB) ligand (RANKL) and macrophage colony-stimulating factor (M-CSF) in mouse RAW 264.7 cells. The results showed that Rb2 dose-dependently inhibited the formation of the tartrate resistant acid phosphatase (TRAP)-positive multinucleated cells and TRAP expression. Furthermore, Rb2 promoted osteoprotegerin expression and bone resorption. The expression of osteoclast marker genes including nuclear factor of activated T cells c1 (NFATc1), c-Fos, OSCAR, and cathepsin K were also markedly inhibited by Rb2 treatment. Moreover, Rb2 significantly inhibited the RANKL-induced NF-κB activation. In addition, Rb2 also markedly suppressed the activation of signal transducer and activator of transcription protein 3 (STAT3) signaling pathway. Interestingly, the knockdown of STAT3 significantly strengthened the inhibitory effect of Rb2 on osteoclast differentiation. Taken together, our study suggests that Rb2 inhibits osteoclast differentiation associated with blocking NF-κB and STAT3 signaling pathways.
人参皂苷 -Rb2（Rb2）是从人参中提取的一种20（S）-原人参二醇糖苷，具有多种生物活性，在骨代谢领域引起了相当大的关注。然而，Rb2对破骨细胞分化的影响尚不清楚。在本研究中，我们旨在探讨Rb2在调节破骨细胞分化中的潜在作用及其潜在的分子机制。在小鼠RAW 264.7细胞中，通过核因子 -κB受体激活剂配体（RANKL）和巨噬细胞集落刺激因子（M-CSF）诱导破骨细胞分化。结果表明，Rb2呈剂量依赖性抑制抗酒石酸酸性磷酸酶（TRAP）阳性多核细胞的形成和TRAP表达。此外，Rb2促进骨保护素表达并抑制骨吸收。Rb2处理还显著抑制了包括活化T细胞核因子c1（NFATc1）、c-Fos、OSCAR和组织蛋白酶K在内的破骨细胞标记基因的表达。此外，Rb2显著抑制RANKL诱导的NF-κB激活。另外，Rb2也显著抑制信号转导子和转录激活子蛋白3（STAT3）信号通路的激活。有趣的是，敲低STAT3显著增强了Rb2对破骨细胞分化的抑制作用。综上所述，我们的研究表明，Rb2通过阻断NF-κB和STAT3信号通路抑制破骨细胞分化。
