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dc.contributor.author
Öztürk, Ece
dc.contributor.author
Hobiger, Stefanie
dc.contributor.author
Despot-Slade, Evelin
dc.contributor.author
Pichler, Michael
dc.contributor.author
Zenobi-Wong, Marcy
dc.date.accessioned
2017-12-05T11:59:29Z
dc.date.available
2017-10-06T01:51:38Z
dc.date.available
2017-10-23T13:31:20Z
dc.date.available
2017-12-05T11:59:29Z
dc.date.issued
2017
dc.identifier.other
10.1038/s41598-017-09505-6
en_US
dc.identifier.uri
http://hdl.handle.net/20.500.11850/190234
dc.identifier.doi
10.3929/ethz-b-000190234
dc.description.abstract
Cartilage tissue is avascular and hypoxic which regulates chondrocyte phenotype via stabilization of HIFs. Here, we investigated the role of hypoxia and HIFs in regulation of Rho and canonical Wnt signaling in chondrocytes. Our data demonstrates that hypoxia controls the expression of RhoA in chondrocytes in a context-dependent manner on the culturing conditions. Within a 3D microenvironment, hypoxia suppresses RhoA on which hypoxia-driven expression of chondrogenic markers depends. Conversely, hypoxia leads to upregulation of RhoA in chondrocytes on 2D with a failure in re-expression of chondrogenic markers. Similarly to RhoA, hypoxic regulation of Wnt/β-catenin signaling depends on the microenvironment. Hypoxia downregulates β-catenin within 3D hydrogels whereas it causes a potent increase on 2D. Hypoxia-induced suppression of canonical Wnt signaling in 3D contributes to the promotion of chondrogenic phenotype as induction of Wnt signaling abrogates the hypoxic re-differentiation of chondrocytes. Inhibiting Wnt/β-catenin signaling via stabilization of Axin2 leads to a synergistic enhancement of hypoxia-induced expression of chondrogenic markers. The effects of hypoxia on Rho and Wnt/β-catenin signaling are HIF-dependent as stabilizing HIFs under normoxia revealed similar effects on chondrocytes. The study reveals important insights on hypoxic signaling of chondrocytes and how hypoxia regulates cellular mechanisms depending on the cellular microenvironment.
en_US
dc.language.iso
en
en_US
dc.publisher
Nature Publishing Group
en_US
dc.rights.uri
http://creativecommons.org/licenses/by/4.0/
dc.title
Hypoxia regulates RhoA and Wnt/beta-catenin signaling in a context-dependent way to control re-differentiation of chondrocytes
en_US
dc.type
Journal Article
dc.rights.license
Creative Commons Attribution 4.0 International
dc.date.published
2017-08-22
ethz.journal.title
Scientific Reports
ethz.journal.volume
7
en_US
ethz.pages.start
9032
en_US
ethz.size
11 p.
en_US
ethz.version.deposit
publishedVersion
en_US
ethz.identifier.wos
ethz.identifier.scopus
ethz.publication.place
London
en_US
ethz.publication.status
published
en_US
ethz.leitzahl
ETH Zürich::00002 - ETH Zürich::00012 - Lehre und Forschung::00007 - Departemente::02070 - Dep. Gesundheitswiss. und Technologie / Dep. of Health Sciences and Technology::02518 - Institut für Biomechanik / Institute for Biomechanics::03949 - Zenobi-Wong, Marcy / Zenobi-Wong, Marcy
ethz.leitzahl.certified
ETH Zürich::00002 - ETH Zürich::00012 - Lehre und Forschung::00007 - Departemente::02070 - Dep. Gesundheitswiss. und Technologie / Dep. of Health Sciences and Technology::02518 - Institut für Biomechanik / Institute for Biomechanics::03949 - Zenobi-Wong, Marcy / Zenobi-Wong, Marcy
ethz.date.deposited
2017-10-06T01:52:02Z
ethz.source
WOS
ethz.eth
yes
en_US
ethz.availability
Open access
en_US
ethz.rosetta.installDate
2017-10-23T13:31:28Z
ethz.rosetta.lastUpdated
2019-01-02T11:07:16Z
ethz.rosetta.exportRequired
true
ethz.rosetta.versionExported
true
ethz.COinS
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