Zhou Feng, Shen Yi, Liu Bo, Chen Xia, Wan Lu, Peng Dan
Department of Orthopaedics, The Second Xiangya Hospital, Central South University, No.139 Middle Renmin Road, Changsha, Hunan 410011, PR China.
Department of Orthopaedics, The Second Xiangya Hospital, Central South University, No.139 Middle Renmin Road, Changsha, Hunan 410011, PR China.
Biochem Biophys Res Commun. 2017 Mar 18;484(4):820-826. doi: 10.1016/j.bbrc.2017.01.179. Epub 2017 Feb 2.
Bone is a rigid yet dynamic organ, and this dynamism is mediated by the delicate balance between osteoclastic bone resorption and osteoblastic bone formation. However, excessive activation of osteoclasts is responsible for many bone diseases such as osteoporosis, Paget disease, and tumor bone metastasis. Agents that could inhibit osteoclast formation or function are regarded as promising alternatives to treat osteoclast-related diseases. Recently, traditional Chinese medicine has attracted attention because of its multiple activities in bone metabolism. Among them, gastrodin has been reported as an anti-osteoporosis agent that reduces reactive oxygen species. However, the direct action of gastrodin on osteoclast differentiation and bone resorption, and its underlying molecular mechanism, remain unknown. In this study, we investigated the effects of gastrodin on receptor activator NF-κB ligand (RANKL)-activated osteoclasts formation and bone resorption. Our results showed that gastrodin retarded RANKL-induced osteoclast differentiation efficiently by downregulating transcriptional and translational expression of nuclear factor of activated T cells cl (NFATc1), a major factor in RANKL-mediated osteoclastogenesis. Meanwhile, gastrodin prevented osteoclast maturation and migration by inhibiting the gene expression of dendrocyte expressed seven transmembrane protein (DC-STAMP), an osteoclastic-specific gene that controls cells fusion and movement. And gastrodin prevented RANKL-induced osteoclastic bone erosion in vitro. In addition, gastrodin also stimulated bone mesenchymal stem cell (BMSC) spreading and osseointegration in titanium plate. In summary, gastrodin could prevent osteoclasts formation and bone resorption via blockage of NFATc1 activity, and stimulate osseointegration in vitro. Gastrodin could be developed as a potent phytochemical candidate to treat osteolytic diseases.
骨骼是一个坚硬但具有动态性的器官，这种动态性由破骨细胞介导的骨吸收和成骨细胞介导的骨形成之间的微妙平衡所调节。然而，破骨细胞的过度活化是导致许多骨骼疾病的原因，如骨质疏松症、佩吉特病和肿瘤骨转移。能够抑制破骨细胞形成或功能的药物被认为是治疗破骨细胞相关疾病的有前景的替代方案。近年来，中药因其在骨代谢中的多种作用而受到关注。其中，天麻素已被报道为一种可减少活性氧的抗骨质疏松药物。然而，天麻素对破骨细胞分化和骨吸收的直接作用及其潜在分子机制仍不清楚。在本研究中，我们研究了天麻素对核因子κB受体活化因子配体（RANKL）激活的破骨细胞形成和骨吸收的影响。我们的结果表明，天麻素通过下调活化T细胞核因子c1（NFATc1）的转录和翻译表达，有效地抑制了RANKL诱导的破骨细胞分化，NFATc1是RANKL介导的破骨细胞生成中的一个主要因子。同时，天麻素通过抑制树突状细胞表达的七跨膜蛋白（DC-STAMP）的基因表达，阻止破骨细胞成熟和迁移，DC-STAMP是一种控制破骨细胞融合和运动的破骨细胞特异性基因。并且天麻素在体外可防止RANKL诱导的破骨细胞性骨侵蚀。此外，天麻素还可刺激骨间充质干细胞（BMSC）在钛板上的铺展和骨整合。总之，天麻素可通过阻断NFATc1活性来防止破骨细胞形成和骨吸收，并在体外刺激骨整合。天麻素可被开发成为一种治疗溶骨性疾病的有效植物化学候选药物。
