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

作者：Yoon Haejin; Kim Hye Lim; Chun Yang Sook; Shin Dong Hoon; Lee Kyoung Hwa; Shin Chan Soo; Lee Dong Yeon; Kim Hong Hee; Lee Zang Hee; Ryoo Hyun Mo; Lee Mi Ni; Oh Goo Taeg^*; Park Jong Wan

来源：Nature Communications, 2014, 5(1): 5176.

DOI：10.1038/ncomms6176

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 CBF beta 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.

• 出版日期2014-11