title: AMP-activated protein kinase regulates thyroid hormone-stimulated osteocalcin synthesis in osteoblasts.
abstract: AMP-activated protein kinase (AMPK) is recognized as a main regulator of energy homeostasis. Osteocalcin (OC), which is produced specifically by mature osteoblasts, is stored in bone matrix, strongly binds to hydroxyapatite and is released into the circulation, has been recognized as a marker of bone metabolism. It has recently been shown that OC released from osteoblasts influences energy metabolism as a hormone. We previously reported that triiodothyronine (T3) stimulates the synthesis of OC in osteoblast-like MC3T3-E1 cells. In the present study, we investigated whether AMPK participates in T3-stimulated OC synthesis in osteoblasts. T3 time-dependently induced the phosphorylation of the AMPKα-subunit (Thr-172), whereas T3 failed to induce the phosphorylation of AMPKα-subunit (Ser-485), AMPKβ-subunit (Ser-108) and AMPKβ-subunit (Ser-182). Both the release and the mRNA expression of OC induced by T3 were significantly inhibited by compound C, an AMPK inhibitor. Compound C suppressed the T3-induced phosphorylation of acetyl-CoA carboxylase, a direct substrate of AMPK. T3-stimulated OC release was significantly reduced in AMPK-knockdown cells using AMPK-siRNA. These results strongly suggest that AMPK positively regulates T3-stimulated OC synthesis in osteoblasts.
authors.affiliation: Department of Orthopedic Surgery, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Kondo
authors.forename: Takanobu
authors.initials: T
authors.lastname: Otsuka
authors.forename: Kenji
authors.initials: K
authors.lastname: Kato
authors.forename: Rie
authors.initials: R
authors.lastname: Matsushima-Nishiwaki
authors.forename: Gen
authors.initials: G
authors.lastname: Kuroyanagi
authors.forename: Jun
authors.initials: J
authors.lastname: Mizutani
authors.forename: Haruhiko
authors.initials: H
authors.lastname: Tokuda
authors.forename: Osamu
authors.initials: O
authors.lastname: Kozawa
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism*; D000103:Acetyl-CoA Carboxylase / Q000378:metabolism; D000818:Animals; D002460:Cell Line; D005786:Gene Expression Regulation / Q000187:drug effects; D051379:Mice; D010006:Osteoblasts / Q000187:drug effects* / Q000378:metabolism*; D015675:Osteocalcin / Q000096:biosynthesis* / Q000235:genetics; D010766:Phosphorylation / Q000187:drug effects; D011720:Pyrazoles / Q000494:pharmacology; D011743:Pyrimidines / Q000494:pharmacology; D034622:RNA Interference; D013963:Thyroid Hormones / Q000494:pharmacology*; D014284:Triiodothyronine / Q000494:pharmacology
chemical_list: D011720:Pyrazoles; D011743:Pyrimidines; D013963:Thyroid Hormones; D014284:Triiodothyronine; D015675:Osteocalcin; C516138:dorsomorphin; D055372:AMP-Activated Protein Kinases; D000103:Acetyl-CoA Carboxylase