Ferulic acid attenuates osteoporosis induced by glucocorticoid through regulating the GSK-3β/Lrp-5/ERK signalling pathways

Abstract

Abstract Objective To evaluate in-vivo and in-vitro effects of ferulic acid (FA) on glucocorticoid-induced osteoarthritis (GIO) to establish its possible underlying mechanisms. Methods The effects of FA on cell proliferation, cell viability (MTT assay), ALP activity, and mineralization assay, and oxidative stress markers (ROS, SOD, GSH LDH and MDA levels) were investigated by MC3T3-E1 cell line. Wistar rats received standard saline (control group) or dexamethasone (GC, 2 mg−1 kg) or DEX+FA (50 and 100 mg−1 kg) orally for 8 weeks. Bone density, micro-architecture, bio-mechanics, bone turnover markers and histo-morphology were determined. The expression of OPG, RANKL, osteogenic markers, and other signalling proteins was assessed employing quantitative RT-PCR and Western blotting. Results The findings indicated the elevation of ALP mRNA expressions, osteogenic markers (Runx-2, OSX, Col-I, and OSN), and the β-Catenin, Lrp-5 and GSK-3β protein expressions. FA showed the potential to increase MC3T3-E1 cell differentiation, proliferation, and mineralization. FA increased oxidative stress markers (SOD, MDA, and GSH) while decreasing ROS levels and lactate dehydrogenase release in GIO rats. The OPG/RANKL mRNA expression ratio was increased by FA, followed by improved GSK-3β and ERK phosphorylation with enhanced mRNA expressions of Lrp-5 and β-catenin. Conclusion These findings showed that FA improved osteoblasts proliferation with oxidative stress suppression by controlling the Lrp-5/GSK-3β/ERK pathway in GIO, demonstrating the potential pathways involved in the mechanism of actions of FA in GIO therapy.