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DNA-PKcs-SIN1 complexation mediates low-dose X-ray irradiation (LDI)-induced Akt activation and osteoblast differentiation

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机构: [a]The Department of Orthopedics, The Second Affiliated Hospital of Soochow University, Suzhou 215000, China [b]Jiangsu Key Laboratory of Translational Research and Therapy for Neuro-Psycho-Diseases and Institute of Neuroscience, Soochow University, Suzhou, Jiangsu 215021, China [c]The Center of Diagnosis and Treatment for Children’s Bone Diseases, The Children’s Hospital Affiliated to Soochow University, Suzhou, Jiangsu 215000, China
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关键词: Low-dose irradiation (LDI) Osteoblast differentiation DNA-PKcs mTORC2-SIN1 and Akt

摘要:
Low-dose irradiation (LDI) induces osteoblast differentiation, however the underlying mechanisms are not fully understood. In this study, we explored the potential role of DNA-dependent protein kinase catalytic subunit (DNA-PKcs)-Akt signaling in LDI-induced osteoblast differentiation. We confirmed that LDI promoted mouse calvarial osteoblast differentiation, which was detected by increased alkaline phosphatase (ALP) activity as well as mRNA expression of type I collagen (Col 1) and runt-related transcription factor 2 (Runx2). In mouse osteoblasts, LDI (1 Gy) induced phosphorylation of DNA-PKcs and Akt (mainly at Ser-473). The kinase inhibitors against DNA-PKcs (NU-7026 and NU-7441) or Akt (LY294002, perifosine and MK-2206), as well as partial depletion of DNA-PKcs or Akt1 by targeted-shRNA, dramatically inhibited LDI-induced Akt activation and mouse osteoblast differentiation. Further, siRNA-knockdown of SIN1, a key component of mTOR complex 2 (mTORC2), also inhibited LDI-induced Akt Ser-473 phosphorylation as well as ALP activity increase and Col I/Runx2 expression in mouse osteoblasts. Co-immunoprecipitation (Co-IP) assay results demonstrated that LDI-induced DNA-PKcs-SIN1 complexation, which was inhibited by NU-7441 or SIN1 siRNA-knockdown in mouse osteoblasts. In summary, our data suggest that DNA-PKcs-SIN1 complexation-mediated Akt activation (Ser-473 phosphorylation) is required for mouse osteoblast differentiation. (C) 2014 Elsevier Inc. All rights reserved.

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出版当年[2013]版:
大类 | 3 区 生物
小类 | 4 区 生化与分子生物学 4 区 生物物理
最新[2023]版:
大类 | 3 区 生物学
小类 | 3 区 生物物理 4 区 生化与分子生物学
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出版当年[2012]版:
Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY Q3 BIOPHYSICS
最新[2023]版:
Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY Q3 BIOPHYSICS

影响因子: 最新[2023版] 最新五年平均 出版当年[2012版] 出版当年五年平均 出版前一年[2011版] 出版后一年[2013版]

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第一作者机构: [a]The Department of Orthopedics, The Second Affiliated Hospital of Soochow University, Suzhou 215000, China
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通讯机构: [c]The Center of Diagnosis and Treatment for Children’s Bone Diseases, The Children’s Hospital Affiliated to Soochow University, Suzhou, Jiangsu 215000, China [*]The Department of Orthopedics, The Second Affiliated Hospital of Soochow University, San-xiang Road, Suzhou 215000, China.
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