Abstract

Osteoporosis (OP) is a frequent orthopedic disease characterized by pain, fractures and deformities. Glucocorticoids are the most common cause of secondary osteoporosis. Here, we aim to explore the function and mechanism of STK11 in glucocorticoid (GC)-induced OP. Human mesenchymal stromal cells (hMSCs) were differentiated under osteogenic or adipogenic culture medium. An in-vitro OP model was induced by dexamethasone (DEX). The viability, differentiation, apoptosis, and ROS level were evaluated for investigating the functions of SKT11 on hMSCs. The SIRT1 inhibitor EX-527, PGC1α inhibitor SR-18292, and AMPK activator metformin were administered into hMSCs for confirming the mechanism of SKT11. Our results showed that STK11 was down-regulated in OP tissues, as well as DEX-treated hMSCs. Overexpressing STK11 attenuated DEX-mediated inhibition of osteogenic differentiation and heightened the activation of the AMPK/SIRT1/PGC1α pathway, whereas STK11 knockdown exerted opposite effects. Inhibiting SIRT1 or PGC1α repressed the promotive effect of STK11 on osteogenic differentiation of hMSCs, while activation of AMPK abated the inhibitory effect of STK11 knockdown on osteogenic differentiation of hMSCs. In conclusion, this study revealed that overexpressing STK11 dampened GC-induced OP by activating the AMPK/SIRT1/PGC1α axis.