RE1-Silencing Transcription Factor (Rest) is a Novel Regulator of Osteoblast Differentiation.
RE1-Silencing Transcription Factor (Rest) is a Novel Regulator of Osteoblast Differentiation.
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RE1-沉默转录因子（休息）是成骨细胞分化的新型调节剂。
DOI：
10.1002/jcb.25148
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发表时间：
2015
影响因子：
4
通讯作者：
Mohan,Subburaman
中科院分区：
文献类型：
--
作者：
Liu,Bo;Cheng,Shaohong;Xing,Weirong;Pourteymoor,Sheila;Mohan,Subburaman
RE1‐silencing transcription factor (Rest) has been identified as a master negative regulator of neuronal differentiation. Nothing is known aboutRestfunction in bone cells. In this study, we examined theRestexpression levels and role during osteoblast differentiation. We found thatRestis abundantly expressed in bone marrow stromal cells, calvarial osteoblasts, and MC3T3‐E1 osteoblasts. Treatment of primary osteoblasts with ascorbic acid (AA) down regulatedRestmRNA expression at an early stage, but not in later stages of differentiation. Consistent with treatment of primary cultures, AA treatment of MC3T3‐E1 cells significantly reducedRestprotein expression at day 3 and at day 8 after initiation of osteoblast differentiation. Treatment of bone marrow stromal cells with BMP‐2 and dexamethasone, but not IGF‐I for 3 days greatly decreasedRestmRNA expression. To test the function ofRestduring osteoblast differentiation,Restexpression was knocked down in MC3T3‐E1 cell subclones segregated on the basis of ALP activity (differentiation status) using lentivirus expressing shRNA againstRest. An 80% knockdown ofRestexpression decreasedOsterix(Osx) expression by 52–57% and as a result, increased both basal and AA induced ALP expression and activity in the subclone that expresses low basal level of ALP (undifferentiated). By contrast, a 98% knockdown ofRestexpression in cells that express high basal levels of ALP (differentiated cells) caused a significant reduction inOsxexpression, basal and AA induced ALP expression and activity. These data suggest thatRestregulates early osteoblast differentiation via modulatingRestexpression that is independent ofOsxexpression. J. Cell. Biochem. 116: 1932–1938, 2015. © 2015 Wiley Periodicals, Inc.
