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Published on: February 28, 2017
NAA10 controls osteoblast differentiation and bone formation as a feedback regulator of Runx2
Haejin Yoon1, Hye-Lim Kim2, Yang-Sook Chun3
11] 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.
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.
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