First Author | Yoon H | Year | 2014 |
Journal | Nat Commun | Volume | 5 |
Pages | 5176 | PubMed ID | 25376646 |
Mgi Jnum | J:276208 | Mgi Id | MGI:6296454 |
Doi | 10.1038/ncomms6176 | Citation | Yoon H, et al. (2014) NAA10 controls osteoblast differentiation and bone formation as a feedback regulator of Runx2. Nat Commun 5:5176 |
abstractText | Runt-related transcription factor 2 (Runx2) transactivates many genes required for osteoblast differentiation. The role of N-alpha-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 CBFbeta 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. |