NAA10 controls osteoblast differentiation and bone formation as a feedback regulator of Runx2.
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.
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.
Haejin
H
Yoon
Department of Pharmacology, Seoul National University College of Medicine, Seoul 110-799, Korea.
Hye-Lim
HL
Kim
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.
Yang-Sook
YS
Chun
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.
Dong Hoon
DH
Shin
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.
Kyoung-Hwa
KH
Lee
Department of Internal Medicine, Seoul National University College of Medicine, Seoul 110-799, Korea.
Chan Soo
CS
Shin
Department of Orthopedic Surgery, Seoul National University College of Medicine, Seoul 110-799, Korea.
Dong Yeon
DY
Lee
Department of Cell and Developmental Biology, Seoul National University School of Dentistry, Seoul 110-749, Korea.
Hong-Hee
HH
Kim
Department of Cell and Developmental Biology, Seoul National University School of Dentistry, Seoul 110-749, Korea.
Zang Hee
ZH
Lee
Department of Molecular Genetics, Seoul National University School of Dentistry, Seoul 110-749, Korea.
Hyun-Mo
HM
Ryoo
Department of Life Science, Ewha Womans University, Seoul 120-750, Korea.
Mi-Ni
MN
Lee
Department of Life Science, Ewha Womans University, Seoul 120-750, Korea.
Goo Taeg
GT
Oh
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.
Jong-Wan
JW
Park
D000595:Amino Acid Sequence; D000818:Animals; D001861:Bone Regeneration / Q000502:physiology; D002454:Cell Differentiation / Q000502:physiology*; D002478:Cells, Cultured; D050659:Core Binding Factor Alpha 1 Subunit / Q000502:physiology*; D025461:Feedback, Physiological / Q000502:physiology*; D005260:Female; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D063209:N-Terminal Acetyltransferase A / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D063213:N-Terminal Acetyltransferase E / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D063206:N-Terminal Acetyltransferases / Q000172:deficiency / Q000235:genetics / Q000502:physiology; D010006:Osteoblasts / Q000166:cytology* / Q000502:physiology; D010012:Osteogenesis / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000502:physiology; D012886:Skull / Q000293:injuries / Q000502:physiology; D014945:Wound Healing / Q000502:physiology
D050659:Core Binding Factor Alpha 1 Subunit; C000604993:N-alpha-acetyltransferase 10, rat; C493716:Runx2 protein, mouse; C493717:Runx2 protein, rat; D063209:N-Terminal Acetyltransferase A; C508558:Naa10 protein, mouse; D063213:N-Terminal Acetyltransferase E; D063206:N-Terminal Acetyltransferases