PMID- 26950191
OWN - NLM
STAT- MEDLINE
DCOM- 20170911
LR  - 20180118
IS  - 1557-8534 (Electronic)
IS  - 1547-3287 (Linking)
VI  - 25
IP  - 9
DP  - 2016 May 1
TI  - Loss-of-Function of HtrA1 Abrogates All-Trans Retinoic Acid-Induced Osteogenic 
      Differentiation of Mouse Adipose-Derived Stromal Cells Through Deficiencies in 
      p70S6K Activation.
PG  - 687-98
LID - 10.1089/scd.2015.0368 [doi]
AB  - All-trans retinoic acid (ATRA) is a potent inducer of osteogenic differentiation 
      in mouse adipose-derived stromal cells (mASCs), although the underlying 
      mechanisms responsible for its mode of action have yet to be completely 
      elucidated. High temperature requirement protease A1 (HtrA1) is a newly 
      recognized modulator of human multipotent stromal cell (MSC) osteogenesis and as 
      such, may play a role in regulating ATRA-dependent osteogenic differentiation of 
      mASCs. In this study, we assessed the influence of small interfering RNA 
      (siRNA)-induced repression of HtrA1 production on mASC osteogenesis and examined 
      its effects on ATRA-mediated mammalian target of rapamycin (mTOR) signaling. 
      Inhibition of HtrA1 production in osteogenic mASCs resulted in a significant 
      reduction of alkaline phosphatase activity and mineralized matrix formation. 
      Western blot analyses revealed the rapid activation of Akt (Ser473) and p70S6K 
      (Thr389) in ATRA-treated mASCs, and that levels of phosphorylated p70S6K were 
      noticeably reduced in HtrA1-deficient mASCs. Further studies using mTOR inhibitor 
      rapamycin and siRNA specific for the p70S6K gene Rps6kb1 confirmed ATRA-mediated 
      mASC osteogenesis as being dependent on p70S6K activation. Finally, transfection 
      of cells with a constitutively active rapamycin-resistant p70S6K mutant could 
      restore the mineralizing capacity of HtrA1-deficient mASCs. These findings 
      therefore lend further support for HtrA1 as a positive mediator of MSC 
      osteogenesis and provide new insights into the molecular mode of action of ATRA 
      in regulating mASC lineage commitment.
FAU - Glanz, Stephan
AU  - Glanz S
AD  - 1 Bone and Stem Cell Research Group, CABMM, University of Zurich , Zurich, 
      Switzerland .
AD  - 2 Zurich Center for Integrative Human Physiology (ZIHP), University of Zurich , 
      Zurich, Switzerland .
FAU - Mirsaidi, Ali
AU  - Mirsaidi A
AD  - 1 Bone and Stem Cell Research Group, CABMM, University of Zurich , Zurich, 
      Switzerland .
FAU - Lopez-Fagundo, Cristina
AU  - Lopez-Fagundo C
AD  - 1 Bone and Stem Cell Research Group, CABMM, University of Zurich , Zurich, 
      Switzerland .
FAU - Filliat, Gladys
AU  - Filliat G
AD  - 1 Bone and Stem Cell Research Group, CABMM, University of Zurich , Zurich, 
      Switzerland .
AD  - 2 Zurich Center for Integrative Human Physiology (ZIHP), University of Zurich , 
      Zurich, Switzerland .
FAU - Tiaden, Andre N
AU  - Tiaden AN
AD  - 1 Bone and Stem Cell Research Group, CABMM, University of Zurich , Zurich, 
      Switzerland .
FAU - Richards, Peter J
AU  - Richards PJ
AD  - 1 Bone and Stem Cell Research Group, CABMM, University of Zurich , Zurich, 
      Switzerland .
AD  - 2 Zurich Center for Integrative Human Physiology (ZIHP), University of Zurich , 
      Zurich, Switzerland .
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20160411
PL  - United States
TA  - Stem Cells Dev
JT  - Stem cells and development
JID - 101197107
RN  - 5688UTC01R (Tretinoin)
RN  - EC 2.7.11.1 (Ribosomal Protein S6 Kinases, 70-kDa)
RN  - EC 3.4.21.- (High-Temperature Requirement A Serine Peptidase 1)
RN  - EC 3.4.21.- (HtrA1 protein, mouse)
RN  - EC 3.4.21.- (Serine Endopeptidases)
RN  - W36ZG6FT64 (Sirolimus)
SB  - IM
MH  - Adipose Tissue/*cytology
MH  - Animals
MH  - Blotting, Western
MH  - Cell Differentiation/*drug effects
MH  - Enzyme Activation/drug effects
MH  - Gene Knockdown Techniques
MH  - High-Temperature Requirement A Serine Peptidase 1
MH  - Mice
MH  - Models, Biological
MH  - Mutation/genetics
MH  - Osteogenesis/*drug effects
MH  - Ribosomal Protein S6 Kinases, 70-kDa/*metabolism
MH  - Serine Endopeptidases/*deficiency/metabolism
MH  - Sirolimus/pharmacology
MH  - Stromal Cells/cytology/drug effects/enzymology
MH  - Tretinoin/*pharmacology
EDAT- 2016/03/08 06:00
MHDA- 2017/09/12 06:00
CRDT- 2016/03/08 06:00
PHST- 2016/03/08 06:00 [entrez]
PHST- 2016/03/08 06:00 [pubmed]
PHST- 2017/09/12 06:00 [medline]
AID - 10.1089/scd.2015.0368 [doi]
PST - ppublish
SO  - Stem Cells Dev. 2016 May 1;25(9):687-98. doi: 10.1089/scd.2015.0368. Epub 2016 
      Apr 11.