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Osteoblast differentiation is functionally associated with decreased AMP kinase activity

Authors

  • Takayuki Kasai,

    1. Department of Oral Biochemistry, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan
    2. Department of Oral Maxillofacial Prosthodontics, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan
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  • Kenjiro Bandow,

    1. Department of Oral Biochemistry, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan
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  • Hiraku Suzuki,

    1. Department of Oral Biochemistry, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan
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  • Norika Chiba,

    1. Department of Oral Biochemistry, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan
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  • Kyoko Kakimoto,

    1. Department of Oral Biochemistry, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan
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  • Tomokazu Ohnishi,

    1. Department of Oral Biochemistry, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan
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  • Shin-ichiro Kawamoto,

    1. Department of Oral Maxillofacial Prosthodontics, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan
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  • Eiichi Nagaoka,

    1. Department of Oral Maxillofacial Prosthodontics, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan
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  • Tetsuya Matsuguchi

    Corresponding author
    1. Department of Oral Biochemistry, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan
    • Department of Oral Biochemistry, Graduate School of Medical and Dental Sciences, Kagoshima University, 8-35-1 Sakuragaoka, Kagoshima 890-8544, Japan.
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Abstract

Osteoblasts, originating from mesenchymal stem cells, play a pivotal role in bone formation and mineralization. Several transcription factors including runt-related transcription factor 2 (Runx2) have been reported to be essential for osteoblast differentiation, whereas the cytoplasmic signal transduction pathways controlling the differentiation process have not been fully elucidated. AMP-activated protein kinase (AMPK) is a serine–threonine kinase generally regarded as a key regulator of cellular energy homeostasis, polarity, and division. Recent lines of evidence have indicated that the activity of the catalytic α subunit of AMPK is regulated through its phosphorylation by upstream AMPK kinases (AMPKKs) including LKB1. Here, we explored the role of AMPK in osteoblast differentiation using in vitro culture models. Phosphorylation of AMPKα was significantly decreased during osteoblastic differentiation in both primary osteoblasts and MC3T3-E1, a mouse osteoblastic cell line. Conversely, the terminal differentiation of primary osteoblasts and MC3T3-E1 cells, represented by matrix mineralization, was significantly inhibited by glucose restriction and stimulation with metformin, both of which are known activators of AMPK. Matrix mineralization of MC3T3-E1 cells was also inhibited by the forced expression of a constitutively active form of AMPKα. Metformin significantly inhibited gene expression of Runx2 along with osteoblast differentiation markers including osteocalcin (Ocn), bone sialo protein (Bsp), and osteopontin (Opn). Thus, our present data indicate that differentiation of osteoblasts is functionally associated with decreased AMPK activity. J. Cell. Physiol. 221: 740–749, 2009. © 2009 Wiley-Liss, Inc.

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