PMID- 28053606
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20201001
IS  - 1687-966X (Print)
IS  - 1687-9678 (Electronic)
VI  - 2016
DP  - 2016
TI  - PS1/gamma-Secretase-Mediated Cadherin Cleavage Induces beta-Catenin Nuclear 
      Translocation and Osteogenic Differentiation of Human Bone Marrow Stromal Cells.
PG  - 3865315
LID - 10.1155/2016/3865315 [doi]
LID - 3865315
AB  - Bone marrow stromal cells (BMSCs) are considered a promising tool for bone 
      bioengineering. However, the mechanisms controlling osteoblastic commitment are 
      still unclear. Osteogenic differentiation of BMSCs requires the activation of 
      beta-catenin signaling, classically known to be regulated by the canonical Wnt 
      pathway. However, BMSCs treatment with canonical Wnts in vitro does not always 
      result in osteogenic differentiation and evidence indicates that a more complex 
      signaling pathway, involving cadherins, would be required to induce beta-catenin 
      signaling in these cells. Here we showed that Wnt3a alone did not induce TCF 
      activation in BMSCs, maintaining the cells at a proliferative state. On the other 
      hand, we verified that, upon BMSCs osteoinduction with dexamethasone, cadherins 
      were cleaved by the PS1/gamma-secretase complex at the plasma membrane, and this 
      event was associated with an enhanced beta-catenin translocation to the nucleus and 
      signaling. When PS1/gamma-secretase activity was inhibited, the osteogenic process 
      was impaired. Altogether, we provide evidence that PS1/gamma-secretase-mediated 
      cadherin cleavage has as an important role in controlling beta-catenin signaling 
      during the onset of BMSCs osteogenic differentiation, as part of a complex 
      signaling pathway responsible for cell fate decision. A comprehensive map of 
      these pathways might contribute to the development of strategies to improve bone 
      repair.
FAU - Bonfim, Danielle C
AU  - Bonfim DC
AUID- ORCID: 0000-0002-6850-2061
AD  - Institute of Biomedical Sciences, Federal University of Rio de Janeiro, Rio de 
      Janeiro, RJ, Brazil; Clementino Fraga Filho University Hospital, Federal 
      University of Rio de Janeiro, Rio de Janeiro, RJ, Brazil.
FAU - Dias, Rhayra B
AU  - Dias RB
AD  - Institute of Biomedical Sciences, Federal University of Rio de Janeiro, Rio de 
      Janeiro, RJ, Brazil; Clementino Fraga Filho University Hospital, Federal 
      University of Rio de Janeiro, Rio de Janeiro, RJ, Brazil.
FAU - Fortuna-Costa, Anneliese
AU  - Fortuna-Costa A
AD  - Clementino Fraga Filho University Hospital, Federal University of Rio de Janeiro, 
      Rio de Janeiro, RJ, Brazil; Institute of Medical Biochemistry, National Institute 
      of Cancer, Rio de Janeiro, RJ, Brazil.
FAU - Chicaybam, Leonardo
AU  - Chicaybam L
AD  - Molecular Carcinogenesis Program, National Institute of Cancer, Rio de Janeiro, 
      RJ, Brazil; Evandro Chagas Clinical Research Institute, Oswaldo Cruz Institute 
      (FIOCRUZ), Rio de Janeiro, RJ, Brazil.
FAU - Lopes, Daiana V
AU  - Lopes DV
AD  - Institute of Biomedical Sciences, Federal University of Rio de Janeiro, Rio de 
      Janeiro, RJ, Brazil; Clementino Fraga Filho University Hospital, Federal 
      University of Rio de Janeiro, Rio de Janeiro, RJ, Brazil.
FAU - Dutra, Helio S
AU  - Dutra HS
AD  - Institute of Biomedical Sciences, Federal University of Rio de Janeiro, Rio de 
      Janeiro, RJ, Brazil; Clementino Fraga Filho University Hospital, Federal 
      University of Rio de Janeiro, Rio de Janeiro, RJ, Brazil.
FAU - Borojevic, Radovan
AU  - Borojevic R
AD  - Institute of Biomedical Sciences, Federal University of Rio de Janeiro, Rio de 
      Janeiro, RJ, Brazil; Clementino Fraga Filho University Hospital, Federal 
      University of Rio de Janeiro, Rio de Janeiro, RJ, Brazil.
FAU - Bonamino, Martin
AU  - Bonamino M
AD  - Molecular Carcinogenesis Program, National Institute of Cancer, Rio de Janeiro, 
      RJ, Brazil.
FAU - Mermelstein, Claudia
AU  - Mermelstein C
AD  - Institute of Biomedical Sciences, Federal University of Rio de Janeiro, Rio de 
      Janeiro, RJ, Brazil.
FAU - Rossi, Maria Isabel D
AU  - Rossi MI
AUID- ORCID: 0000-0003-3432-8453
AD  - Institute of Biomedical Sciences, Federal University of Rio de Janeiro, Rio de 
      Janeiro, RJ, Brazil; Clementino Fraga Filho University Hospital, Federal 
      University of Rio de Janeiro, Rio de Janeiro, RJ, Brazil.
LA  - eng
PT  - Journal Article
DEP - 20161208
PL  - United States
TA  - Stem Cells Int
JT  - Stem cells international
JID - 101535822
PMC - PMC5178376
COIS- All authors state that they have no competing interests.
EDAT- 2017/01/06 06:00
MHDA- 2017/01/06 06:01
PMCR- 2016/12/08
CRDT- 2017/01/06 06:00
PHST- 2016/09/12 00:00 [received]
PHST- 2016/11/01 00:00 [accepted]
PHST- 2017/01/06 06:00 [entrez]
PHST- 2017/01/06 06:00 [pubmed]
PHST- 2017/01/06 06:01 [medline]
PHST- 2016/12/08 00:00 [pmc-release]
AID - 10.1155/2016/3865315 [doi]
PST - ppublish
SO  - Stem Cells Int. 2016;2016:3865315. doi: 10.1155/2016/3865315. Epub 2016 Dec 8.