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AMP-activated protein kinase regulates thyroid hormone-stimulated osteocalcin synthesis in osteoblasts

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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.
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Document Type: Research Article

Affiliations: 1: Department of Orthopedic Surgery, Nagoya City University Graduate School of Medical Sciences, Nagoya 467-8601, Japan 2: Department of Pharmacology, Gifu University Graduate School of Medicine, Gifu 501-1194, Japan 3: Department of Clinical Laboratory, National Hospital for Geriatric Medicine, National Center for Geriatrics and Gerontology, Obu, Aichi 474-8511, Japan

Publication date: January 1, 2013

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  • The International Journal of Molecular Medicine is a monthly, peer-reviewed journal devoted to the publication of high quality studies related to the molecular mechanisms of human disease. The journal welcomes research on all aspects of molecular and clinical research, ranging from biochemistry to immunology, pathology, genetics, human genomics, microbiology, molecular pathogenesis, molecular cardiology, molecular surgery and molecular psychology.

    The International Journal of Molecular Medicine aims to provide an insight for researchers within the community in regard to developing molecular tools and identifying molecular targets for the diagnosis and treatment of a diverse number of human diseases.
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