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

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

doi:10.1038/ncomms6176

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

Nat Commun. 2014 Nov 7:5:5176. doi: 10.1038/ncomms6176.

Authors

Haejin Yoon¹, Hye-Lim Kim², Yang-Sook Chun³, Dong Hoon Shin⁴, Kyoung-Hwa Lee⁵, Chan Soo Shin⁶, Dong Yeon Lee⁷, Hong-Hee Kim⁸, Zang Hee Lee⁸, Hyun-Mo Ryoo⁹, Mi-Ni Lee¹⁰, Goo Taeg Oh¹⁰, Jong-Wan Park¹¹

Affiliations

¹ 1] Department of Biomedical Science, Seoul National University College of Medicine, Seoul 110-799, Korea [2] Department of Pharmacology, Seoul National University College of Medicine, Seoul 110-799, Korea.
² Department of Pharmacology, Seoul National University College of Medicine, Seoul 110-799, Korea.
³ 1] Department of Biomedical Science, Seoul National University College of Medicine, Seoul 110-799, Korea [2] Department of Physiology, Seoul National University College of Medicine, Seoul 110-799, Korea [3] Ischemic/Hypoxic disease Institute, Seoul National University College of Medicine, Seoul 110-799, Korea.
⁴ 1] Department of Pharmacology, Seoul National University College of Medicine, Seoul 110-799, Korea [2] Ischemic/Hypoxic disease Institute, Seoul National University College of Medicine, Seoul 110-799, Korea.
⁵ 1] Department of Physiology, Seoul National University College of Medicine, Seoul 110-799, Korea [2] Ischemic/Hypoxic disease Institute, Seoul National University College of Medicine, Seoul 110-799, Korea.
⁶ Department of Internal Medicine, Seoul National University College of Medicine, Seoul 110-799, Korea.
⁷ Department of Orthopedic Surgery, Seoul National University College of Medicine, Seoul 110-799, Korea.
⁸ Department of Cell and Developmental Biology, Seoul National University School of Dentistry, Seoul 110-749, Korea.
⁹ Department of Molecular Genetics, Seoul National University School of Dentistry, Seoul 110-749, Korea.
¹⁰ Department of Life Science, Ewha Womans University, Seoul 120-750, Korea.
¹¹ 1] Department of Biomedical Science, Seoul National University College of Medicine, Seoul 110-799, Korea [2] Department of Pharmacology, Seoul National University College of Medicine, Seoul 110-799, Korea [3] Ischemic/Hypoxic disease Institute, Seoul National University College of Medicine, Seoul 110-799, Korea.

PMID: 25376646
DOI: 10.1038/ncomms6176

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Amino Acid Sequence
Animals
Bone Regeneration / physiology
Cell Differentiation / physiology*
Cells, Cultured
Core Binding Factor Alpha 1 Subunit / physiology*
Feedback, Physiological / physiology*
Female
Male
Mice
Mice, Knockout
Mice, Transgenic
Molecular Sequence Data
N-Terminal Acetyltransferase A / deficiency
N-Terminal Acetyltransferase A / genetics
N-Terminal Acetyltransferase A / physiology*
N-Terminal Acetyltransferase E / deficiency
N-Terminal Acetyltransferase E / genetics
N-Terminal Acetyltransferase E / physiology*
N-Terminal Acetyltransferases / deficiency
N-Terminal Acetyltransferases / genetics
N-Terminal Acetyltransferases / physiology
Osteoblasts / cytology*
Osteoblasts / physiology
Osteogenesis / physiology*
Rats
Rats, Sprague-Dawley
Signal Transduction / physiology
Skull / injuries
Skull / physiology
Wound Healing / physiology

Substances

Core Binding Factor Alpha 1 Subunit
N-alpha-acetyltransferase 10, rat
Runx2 protein, mouse
Runx2 protein, rat
N-Terminal Acetyltransferase A
Naa10 protein, mouse
N-Terminal Acetyltransferase E
N-Terminal Acetyltransferases