PMID- 26519689
OWN - NLM
STAT- MEDLINE
DCOM- 20160706
LR  - 20160216
IS  - 1097-4652 (Electronic)
IS  - 0021-9541 (Linking)
VI  - 231
IP  - 6
DP  - 2016 Jun
TI  - The Transcription Factor EB (TFEB) Regulates Osteoblast Differentiation Through 
      ATF4/CHOP-Dependent Pathway.
PG  - 1321-33
LID - 10.1002/jcp.25235 [doi]
AB  - Osteoblasts are bone-forming cells that produce large amounts of collagen type I 
      and various bone matrix proteins. Although osteoblast differentiation is highly 
      regulated by various factors, it remains unknown whether lysosomes are directly 
      involved in osteoblast differentiation. Here, we demonstrate the transcription 
      factor EB (TFEB), a master regulator of lysosomal biogenesis, modulates 
      osteoblast differentiation. The expression levels of TFEB as well as those of 
      endosomal/lysosomal proteins were up-regulated during osteoblast differentiation 
      using mouse osteoblastic MC3T3-E1 cells. By gene knockdown (KD) experiments with 
      small interfering RNA (siRNA), TFEB depletion caused markedly reduced osteoblast 
      differentiation as compared with the control cells. Conversely, overexpression 
      (OE) of TFEB resulted in strikingly enhanced osteoblastogenesis compared to the 
      control cells. By analysis of down-stream effector molecules, TFEB KD was found 
      to cause marked up-regulation of activating transcription factor 4 (ATF4) and 
      CCAAT/enhancer-binding protein homologous protein (CHOP), both of which are 
      essential factors for osteoblastogenesis. In contrast, TFEB OE promoted 
      osteoblast differentiation through reduced expression of ATF4 and CHOP without 
      differentiation agents. Given the importance of ATF4 and CHOP in 
      osteoblastogenesis, it is clear that the TFEB-regulated signaling pathway for 
      osteoblast differentiation is involved in ATF4/CHOP-dependent signaling pathway.
CI  - (c) 2015 Wiley Periodicals, Inc.
FAU - Yoneshima, Erika
AU  - Yoneshima E
AD  - Division of Dental Pharmacology, Graduate School of Biomedical Sciences, Nagasaki 
      University, Nagasaki, Japan.
AD  - Division of Orthodontics and Dentofacial Orthopedics, Graduate School of 
      Biomedical Sciences, Nagasaki University, Nagasaki, Japan.
FAU - Okamoto, Kuniaki
AU  - Okamoto K
AD  - Division of Dental Pharmacology, Graduate School of Biomedical Sciences, Nagasaki 
      University, Nagasaki, Japan.
FAU - Sakai, Eiko
AU  - Sakai E
AD  - Division of Dental Pharmacology, Graduate School of Biomedical Sciences, Nagasaki 
      University, Nagasaki, Japan.
FAU - Nishishita, Kazuhisa
AU  - Nishishita K
AD  - Division of Dental Pharmacology, Graduate School of Biomedical Sciences, Nagasaki 
      University, Nagasaki, Japan.
FAU - Yoshida, Noriaki
AU  - Yoshida N
AD  - Division of Orthodontics and Dentofacial Orthopedics, Graduate School of 
      Biomedical Sciences, Nagasaki University, Nagasaki, Japan.
FAU - Tsukuba, Takayuki
AU  - Tsukuba T
AD  - Division of Dental Pharmacology, Graduate School of Biomedical Sciences, Nagasaki 
      University, Nagasaki, Japan.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20151120
PL  - United States
TA  - J Cell Physiol
JT  - Journal of cellular physiology
JID - 0050222
RN  - 0 (Atf4 protein, mouse)
RN  - 0 (BMP2 protein, human)
RN  - 0 (Basic Helix-Loop-Helix Leucine Zipper Transcription Factors)
RN  - 0 (Bone Morphogenetic Protein 2)
RN  - 0 (Ddit3 protein, mouse)
RN  - 0 (Reactive Oxygen Species)
RN  - 0 (Smad1 Protein)
RN  - 0 (Smad1 protein, mouse)
RN  - 0 (Smad5 Protein)
RN  - 0 (Smad5 protein, mouse)
RN  - 0 (Tcfeb protein, mouse)
RN  - 145891-90-3 (Activating Transcription Factor 4)
RN  - 147336-12-7 (Transcription Factor CHOP)
SB  - IM
MH  - 3T3 Cells
MH  - Activating Transcription Factor 4/genetics/*metabolism
MH  - Animals
MH  - Apoptosis
MH  - Basic Helix-Loop-Helix Leucine Zipper Transcription Factors/genetics/*metabolism
MH  - Bone Morphogenetic Protein 2/pharmacology
MH  - *Cell Differentiation/drug effects
MH  - Endosomes/metabolism
MH  - Gene Expression Regulation
MH  - Gene Knockdown Techniques
MH  - Lysosomes/metabolism
MH  - Mice
MH  - Mitochondria/metabolism
MH  - Osteoblasts/drug effects/*metabolism/pathology
MH  - RNA Interference
MH  - Reactive Oxygen Species/metabolism
MH  - *Signal Transduction/drug effects
MH  - Smad1 Protein/genetics/metabolism
MH  - Smad5 Protein/genetics/metabolism
MH  - Transcription Factor CHOP/genetics/*metabolism
MH  - Transfection
EDAT- 2015/11/01 06:00
MHDA- 2016/07/07 06:00
CRDT- 2015/11/01 06:00
PHST- 2015/06/25 00:00 [received]
PHST- 2015/10/29 00:00 [accepted]
PHST- 2015/11/01 06:00 [entrez]
PHST- 2015/11/01 06:00 [pubmed]
PHST- 2016/07/07 06:00 [medline]
AID - 10.1002/jcp.25235 [doi]
PST - ppublish
SO  - J Cell Physiol. 2016 Jun;231(6):1321-33. doi: 10.1002/jcp.25235. Epub 2015 Nov 
      20.