Please use this identifier to cite or link to this item: http://hdl.handle.net/1822/68040

TitleIn vitro temporal HIF‐mediated deposition of osteochondrogenic matrix governed by hypoxia and osteogenic factors synergy
Author(s)Calejo, I.
Costa-Almeida, R.
Reis, R. L.
Gomes, Manuela E.
KeywordsCell modulation
Enthesis
Hedgehog signaling
Hypoxia-inducible factors
Osteogenic supplementation
Hypoxia‐
inducible factors
Hypoxia&#8208
Issue dateNov-2020
PublisherWiley
JournalJournal of Cellular Physiology
CitationCalejo I., Costa-Almeida R., Reis R. L., Gomes M. E. In vitro temporal HIF‐mediated deposition of osteochondrogenic matrix governed by hypoxia and osteogenic factors synergy, Journal Of Cellular Physiology, doi:10.1002/jcp.30138, 2020
Abstract(s)Musculoskeletal interfaces are naturally hypoxic. An understanding of key interactions occurring between different cell populations and their environment is critical for native tissue recapitulation. Here, an enthesis coculture model (preosteoblasts and tendon cells) was used to understand the influence of hypoxia (5% O2) and osteogenic medium (OM) supplementation in cellsâ phenotype modulation. In single cultures, preosteoblasts were found to undergo osteogenic impairment, while tendon cells underwent a maturation process through extracellular matrix (ECM) rescue. When in coâ culture, hypoxia and osteoinduction promoted a temporal chondro/osteogenic pathway activation, as observed by an early deposition of cartilaginous ECM associated with HIF1A stabilization and RUNX2 activation, and later hypertrophic differentiation resulting from HIF2A translocation and SOX9 activation. Moreover, the presence of OM under hypoxia was shown to influence the extracellular ROS/HIF1A interplay. Overall, this study revealed a link between biochemical factors and cellâ cell crosstalk, providing a molecular framework for hypoxic control and modulation of cellsâ fate toward enthesisâ like phenotypes.
TypeArticle
URIhttp://hdl.handle.net/1822/68040
DOI10.1002/jcp.30138
ISSN0021-9541
e-ISSN1097-4652
Publisher versionhttps://onlinelibrary.wiley.com/doi/full/10.1002/jcp.30138
Peer-Reviewedyes
AccessRestricted access (UMinho)
Appears in Collections:3B’s - Artigos em revistas/Papers in scientific journals

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