Huang Weiqi, Zheng Xiaoling, Yang Xiaodong, Fan Shicai
Department of Orthopaedic Trauma, The Third Affiliated Hospital of Southern Medical University, 183 West Zhongshan Avenue, Guangzhou, 510630, People's Republic of China.
Guangdong Provincial Center for Disease Control and Prevention, Panyu District, Guangzhou, 511400, People's Republic of China.
Calcif Tissue Int. 2017 Apr;100(4):392-401. doi: 10.1007/s00223-017-0242-y. Epub 2017 Feb 9.
Saikosaponin-A (SA), a class of native compound with numerous biological activities, may exert protective effect against postmenopausal bone loss. However, it remains unknown whether SA regulates the osteogenic differentiation of bone marrow stromal cells (BMSCs) in the treatment and prevention of osteoporosis. In this study, BMSCs were treated with various concentrations of SA to stimulate osteogenic differentiation over a 14-day period. Additionally, a canonical ovariectomized (OVX) mouse model was used to evaluate the effect of 3-month SA treatment in preventing postmenopausal osteoporosis. In vitro, we found that SA promotes alkaline phosphatase activity/staining and Alizarin red assay, stimulated the expression of osteogenic markers, i.e., runt-related transcription factor 2 (Runx2), osterix, osteopontin, and osteocalcin (OCN) in BMSCs. In vivo, the trabecular number, trabecular thickness, and trabecular bone mineral density of the distal femoral metaphysis were significantly increased in OVX mice treated intraperitoneally with SA for 3 months compared with OVX mice that not treated with SA. Moreover, the expression of Runx2 and OCN in OVX + SA mice was significantly increased than that in OVX mice. Finally, we found that SA activated the WNT/β-catenin pathway and the expression of several downstream genes including T-cell factor-1 and lymphoid enhancer factor-1. Inhibition of WNT/β-catenin pathway by Dickkopf-related protein 1 blocked the positive role of SA on osteogenesis. Therefore, SA promoted the osteogenic differentiation of BMSCs through WNT/β-catenin signaling.
柴胡皂苷A（SA）是一类具有多种生物活性的天然化合物，可能对绝经后骨质流失具有保护作用。然而，在骨质疏松症的治疗和预防中，SA是否调节骨髓间充质干细胞（BMSCs）的成骨分化仍不清楚。在本研究中，用不同浓度的SA处理BMSCs，以在14天的时间内刺激其成骨分化。此外，使用经典的卵巢切除（OVX）小鼠模型来评估3个月SA治疗对预防绝经后骨质疏松症的效果。在体外，我们发现SA促进碱性磷酸酶活性/染色和茜素红测定，刺激成骨标志物即矮小相关转录因子2（Runx2）、osterix、骨桥蛋白和骨钙素（OCN）在BMSCs中的表达。在体内，与未用SA处理的OVX小鼠相比，腹腔注射SA 3个月的OVX小鼠股骨远端干骺端的小梁数量、小梁厚度和小梁骨矿物质密度显著增加。此外，OVX + SA小鼠中Runx2和OCN的表达比OVX小鼠中显著增加。最后，我们发现SA激活了WNT/β-连环蛋白通路以及包括T细胞因子-1和淋巴样增强因子-1在内的几个下游基因的表达。Dickkopf相关蛋白1对WNT/β-连环蛋白通路的抑制阻断了SA对成骨的积极作用。因此，SA通过WNT/β-连环蛋白信号促进BMSCs的成骨分化。
