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

doi:10.1038/ncomms6176

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

Department of Life Science

Research output: Contribution to journal › Article › peer-review

60 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 language	English
Article number	5176
Journal	Nature Communications
Volume	5
DOIs	https://doi.org/10.1038/ncomms6176
State	Published - 2014

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title = "NAA10 controls osteoblast differentiation and bone formation as a feedback regulator of Runx2",

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.",

author = "Haejin Yoon and Kim, {Hye Lim} and Chun, {Yang Sook} and Shin, {Dong Hoon} and Lee, {Kyoung Hwa} and Shin, {Chan Soo} and Lee, {Dong Yeon} and Kim, {Hong Hee} and Lee, {Zang Hee} and Ryoo, {Hyun Mo} and Lee, {Mi Ni} and Oh, {Goo Taeg} and Park, {Jong Wan}",

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doi = "10.1038/ncomms6176",

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AU - Yoon, Haejin

AU - Kim, Hye Lim

AU - Chun, Yang Sook

AU - Shin, Dong Hoon

AU - Lee, Kyoung Hwa

AU - Shin, Chan Soo

AU - Lee, Dong Yeon

AU - Kim, Hong Hee

AU - Lee, Zang Hee

AU - Ryoo, Hyun Mo

AU - Lee, Mi Ni

AU - Oh, Goo Taeg

AU - Park, Jong Wan

PY - 2014

Y1 - 2014

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AB - 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.

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JO - Nature Communications

JF - Nature Communications

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

Abstract

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