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

Research output: Contribution to journalArticlepeer-review

52 Scopus citations

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 CBF 2 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.

Original languageEnglish
Article number5176
JournalNature Communications
Volume5
DOIs
StatePublished - 2014

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