Effect of Akt on the Differentiation into Osteoclasts Caused by RANKL Stimulation

抄録

Orthodontic therapy applies physical stimulation to the compression-side periodontium, which produces inflammatory cytokines and receptor activators of nuclear factor kappa-B ligand (RANKL). With these proteins, osteoclast precursors such as monocytes and macrophages migrate from vessels into the periodontium and then differentiate into osteoclasts, causing bone resorption. Phosphatidylinositol 3-kinase (PI3-kinase) regulates this differentiation into osteoclasts and bone resorption. PDK1(3-phosphoinositide-dependent protein kinase 1) and Akt (protein kinase B) exist downstream of PI3-kinase. Therefore, in order to clarify the involvement of Akt in the differentiation into osteoclasts, we tested the effects of Akt Inhibitor V, RANKL, and the PDK inhibitor, OSU-03012 on the differentiation of RAW264.7 cells into osteoclasts. Both Akt Inhibitor V and OSU-03012 inhibited the differentiation into osteoclasts of RAW264.7 cells stimulated with RANKL. RANKL-induced phosphorylation of Akt (Thr³⁰⁸) was inhibited in RAW264.7 cells by OSU-03012, while RANKL-induced phosphorylation of Akt (Ser⁴⁷³) was not. These results suggest that Akt (Thr³⁰⁸, but not Ser⁴⁷³) exist upstream of the RANKL stimulation in the differentiation cascade of RAW264.7 cells into osteoclasts.