Andrographolide protects BMSCs from dexamethasone-induced cellular dysfunction and promotes bone formation via the PI3K/AKT pathway

Abstract

Osteoporosis is a common metabolic disease with high morbidity and mortality in the elderly, bringing a heavy socioeconomic burden. Excess use of glucocorticoid is the main cause of secondary Osteoporosis, and there are limited therapies for glucocorticoid-induced osteoporosis (GIOP) treatment. In this study, we explored the protective effect of andrographolide (AGP) on dexamethasone (DEX)-induced dysfunction and osteogenic inhibition in vitro and in vivo. The results showed that AGP could alleviate DEX-induced cytotoxicity, apoptosis and senescence in BMSCs. AGP also increased the level of calcium nodules, RUNX2, COL1A1, OCN and ALP in DEX-treated BMSCs, suggesting that AGP promoted osteogenic differentiation. We found that AGP activated PI3K/AKT signaling pathways and the PI3K inhibitor LY294002 reversed the protective effects of AGP. Additionally, in the GIOP mice model, AGP alleviated bone loss in vivo. In conclusion, these results demonstrated that AGP has a protective effect and promoted bone formation against GIOP through PI3K/AKT pathway.