Roles of AMPK in Osteogenic Differentiation

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AMP-activated protein kinase(AMPK) is a kinase responds to mechanical stress. Phosphorylation of AMPKαwas significantly decreased during osteoblastic differentiation in both primary osteoblasts and MC3T3-E1, a mouse osteoblastic cell line. Conversely, the terminal differentiation of primary osteoblasts and MC3T3-E1 cells, represented by matrix mineralization, was significantly inhibited by stimulation with metformin, an activator of AMPK. Matrix mineralization of MC3T3-E1 cells was also inhibited by the forced expression of a constitutively active form of AMPKα. Metformin significantly inhibited gene expression of Runx2 along with osteoblast differentiation markers. Low-intensity pulsed ultrasound (LIPUS), which is used clinically to promote bone fracture healing, decreased AMPKαphosphorylation. Thus, LIPUS may promote osteoblast differentiation through dephosphorylation of AMPK.