title: Regulation by AMP-activated protein kinase of PGE2-induced osteoprotegerin synthesis in osteoblasts.
abstract: 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.
authors.affiliation: Department of Orthopedic Surgery, Nagoya University Graduate School of Medical Sciences, Nagoya, Aichi 467‑8601, Japan.
authors.forename: Shingo
authors.initials: S
authors.lastname: Kainuma
authors.affiliation: Department of Orthopedic Surgery, Nagoya University Graduate School of Medical Sciences, Nagoya, Aichi 467‑8601, Japan.
authors.forename: Takanobu
authors.initials: T
authors.lastname: Otsuka
authors.affiliation: Department of Orthopedic Surgery, Nagoya University Graduate School of Medical Sciences, Nagoya, Aichi 467‑8601, Japan.
authors.forename: Gen
authors.initials: G
authors.lastname: Kuroyanagi
authors.affiliation: Department of Orthopedic Surgery, Nagoya University Graduate School of Medical Sciences, Nagoya, Aichi 467‑8601, Japan.
authors.forename: Naohiro
authors.initials: N
authors.lastname: Yamamoto
authors.affiliation: Department of Pharmacology, Gifu University Graduate School of Medicine, Gifu, Gifu 501‑1194, Japan.
authors.forename: Rie
authors.initials: R
authors.lastname: Matsushima-Nishiwaki
authors.affiliation: Department of Pharmacology, Gifu University Graduate School of Medicine, Gifu, Gifu 501‑1194, Japan.
authors.forename: Osamu
authors.initials: O
authors.lastname: Kozawa
authors.affiliation: Department of Pharmacology, Gifu University Graduate School of Medicine, Gifu, Gifu 501‑1194, Japan.
authors.forename: Haruhiko
authors.initials: H
authors.lastname: Tokuda
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000103:Acetyl-CoA Carboxylase / Q000378:metabolism; D000818:Animals; D002460:Cell Line; D015232:Dinoprostone / Q000494:pharmacology*; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D051379:Mice; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D010006:Osteoblasts / Q000166:cytology / Q000378:metabolism; D053244:Osteoprotegerin / Q000096:biosynthesis* / Q000235:genetics; D010766:Phosphorylation / Q000187:drug effects; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects; D014158:Transcription, Genetic / Q000187:drug effects*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D053244:Osteoprotegerin; D047428:Protein Kinase Inhibitors; D012333:RNA, Messenger; D048031:JNK Mitogen-Activated Protein Kinases; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D048051:p38 Mitogen-Activated Protein Kinases; D055372:AMP-Activated Protein Kinases; D000103:Acetyl-CoA Carboxylase; D015232:Dinoprostone