Gentiopicroside promotes osteogenesis and prevents bone loss in ovariectomized mice by modulation of β-catenin-BMP2 signaling pathway

Abstract Background: Osteoporosis is characterized by increased bone fragility and the drugs used at present to treat osteoporosis can cause adverse reactions. Gentiopicroside (GEN) is widely used in the traditional Chinese medicine thanks to its multiple pharmacological activities including the suppression of osteoclastogenesis. Therefore, the aim of this work was to explore the effect of GEN on bone mesenchymal stem cells (BMSCs) osteogenesis for a potential osteoporosis therapy.Methods: In vitro, BMSCs were exposed to GEN at different doses for 2 weeks, while in vivo, ovariectomized osteoporosis was established in mice and the therapeutic effect of GEN was evaluated for 3 months.Results: Our results in vitro showed that GEN promoted the activity of alkaline phosphatase, increased the calcified nodules in BMSCs and upregulated the osteogenic factors (Runx2, OSX, OCN, OPN, and BMP2). In vivo, GEN strengthened the secretion of Runx2, OCN, and BMP2, increased the level of osteogenic parameters, and accelerated the osteogenesis of BMSCs by activating the BMP pathway and Wnt/β-catenin pathway, effect that was inhibited using the BMP inhibitor Noggin and Wnt/β-catenin inhibitor DKK1. Silencing the β-catenin gene and BMP2 gene blocked the osteogenic differentiation induced by GEN in BMSCs. This block was also observed when only β-catenin was silenced, while the knockout of BMP2 did not affect β-catenin expression induced by GEN. Interpretation.Conclusions: GEN promotes BMSC osteogenesis by regulating β-catenin-BMP signalling, providing a novel strategy in the treatment of osteoporosis.