Glycine Acts Through Estrogen Receptor Alpha to Mediate Estrogen Receptor Signaling, Stimulating Osteogenesis and Attenuating Adipogenesis in Ovariectomized Rats

Scope Glycine is commonly used as an additive in bone health supplements, the activity and differentiation of bone mesenchymal stem cells (BMSCs) are essential to bone metabolism, but the effect of Glycine on bone metabolism and specific mechanism are not fully clarified. Methods and results The ovariectomized rats to evaluate the effects of Glycine on bone quality and quantity is constructed; then used an ER signaling inhibitor (ICI182780) and an ERα deficient BMSCs to explore how Glycine mediated ERα regulating the osteogenic and adipogenic differentiation of BMSCs; furthermore, an autodock analysis is used to assess the affinity of Glycine and ERα. The results show that Glycine significantly moderated bone mass and bone microstructure in ovariectomized rats; Glycine stimulates the osteogenic differentiation and attenuates the adipogenic differentiation in OVX rats and BMSCs, and these effects could be abolished by ICI 182780; further docking experiment showes that Glycine and ERα have a stronger affinity, and finally proves that the impact of Glycine could be blocked by ERα. Conclusion Glycine stimulates osteogenesis and attenuates adipogenesis in ovariectomized rats, which process may involve in ERα mediated ER signaling pathway. Glycine through ERα mediates estrogen receptor signaling stimulating osteogenesis and attenuating adipogenesis.