Regulation by AMP-activated protein kinase of PGE2-induced osteoprotegerin synthesis in osteoblasts.

Adenosine monophosphate-activated protein kinase (AMPK) is currently recognized to act as a key sensing enzyme in the regulation of cellular energy homeostasis. It has been previously demonstrated that prostaglandin E2 (PGE2) stimulates the synthesis of osteoprotegerin (OPG) through the activation of p38 mitogen-activated protein (MAP) kinase, p44/p42 MAP kinase and stress-activated protein kinase/c‑Jun N‑terminal kinase (SAPK/JNK) in osteoblast‑like MC3T3‑E1 cells. In the present study, it was investigated whether AMPK is implicated in the PGE2‑induced OPG synthesis in MC3T3‑E1 cells. PGE2 was observed to induce the phosphorylation of AMPKα (Thr‑172) and AMPKβ (Ser‑108) in a time‑dependent manner. PGE2 additionally induced the phosphorylation of acetyl‑coenzyme A (CoA) carboxylase, a direct substrate of AMPK. Compound C, an inhibitor of AMPK, which attenuated the phosphorylation of acetyl‑CoA carboxylase, significantly suppressed the PGE2‑stimulated OPG release and the mRNA expression level. Compound C failed to affect the PGE2‑stimulated phosphorylation of p38 MAP kinase or p44/p42 MAP kinase. On the contrary, the phosphorylation of SAPK/JNK was markedly attenuated by compound C. The results of the current study suggest that AMPK acts as a positive regulator in PGE2-stimulated OPG synthesis via SAPK/JNK signaling in osteoblasts.