Metformin induces osteoblast differentiation via orphan nuclear receptor SHP-mediated transactivation of Runx2

► Metformin increases AMPK activation in osteoblast cells. ► SHP expression is induced by AMPK-activated USF-1 expression in osteoblast cells. ► AMPK increases Runx2 expression. ► SHP enhances Runx2 transactivity in osteoblast cells.