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NAA10 controls osteoblast differentiation and bone formation as a feedback regulator of Runx2

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  • Haejin Yoon

    (Seoul National University College of Medicine
    Seoul National University College of Medicine)

  • Hye-Lim Kim

    (Seoul National University College of Medicine)

  • Yang-Sook Chun

    (Seoul National University College of Medicine
    Seoul National University College of Medicine
    Ischemic/Hypoxic disease Institute, Seoul National University College of Medicine)

  • Dong Hoon Shin

    (Seoul National University College of Medicine
    Ischemic/Hypoxic disease Institute, Seoul National University College of Medicine)

  • Kyoung-Hwa Lee

    (Seoul National University College of Medicine
    Ischemic/Hypoxic disease Institute, Seoul National University College of Medicine)

  • Chan Soo Shin

    (Seoul National University College of Medicine)

  • Dong Yeon Lee

    (Seoul National University College of Medicine)

  • Hong-Hee Kim

    (Seoul National University School of Dentistry)

  • Zang Hee Lee

    (Seoul National University School of Dentistry)

  • Hyun-Mo Ryoo

    (Seoul National University School of Dentistry)

  • Mi-Ni Lee

    (Ewha Womans University)

  • Goo Taeg Oh

    (Ewha Womans University)

  • Jong-Wan Park

    (Seoul National University College of Medicine
    Seoul National University College of Medicine
    Ischemic/Hypoxic disease Institute, Seoul National University College of Medicine)

Abstract

Runt-related transcription factor 2 (Runx2) transactivates many genes required for osteoblast differentiation. The role of N-α-acetyltransferase 10 (NAA10, arrest-defective-1), originally identified in yeast, remains poorly understood in mammals. Here we report a new NAA10 function in Runx2-mediated osteogenesis. Runx2 stabilizes NAA10 in osteoblasts during BMP-2-induced differentiation, and NAA10 in turn controls this differentiation by inhibiting Runx2. NAA10 delays bone healing in a rat calvarial defect model and bone development in neonatal mice. Mechanistically, NAA10 acetylates Runx2 at Lys225, and this acetylation inhibits Runx2-driven transcription by interfering with CBFβ binding to Runx2. Our study suggests that NAA10 acts as a guard ensuring balanced osteogenesis by fine-tuning Runx2 signalling in a feedback manner. NAA10 inhibition could be considered a potential strategy for facilitating bone formation.

Suggested Citation

  • Haejin Yoon & Hye-Lim Kim & Yang-Sook Chun & Dong Hoon Shin & Kyoung-Hwa Lee & Chan Soo Shin & Dong Yeon Lee & Hong-Hee Kim & Zang Hee Lee & Hyun-Mo Ryoo & Mi-Ni Lee & Goo Taeg Oh & Jong-Wan Park, 2014. "NAA10 controls osteoblast differentiation and bone formation as a feedback regulator of Runx2," Nature Communications, Nature, vol. 5(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:5:y:2014:i:1:d:10.1038_ncomms6176
    DOI: 10.1038/ncomms6176
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