Biomaterials, Biodegradables and Biomimetics Research Group

Papers in Scientific Journals

In vitro temporal HIF‐mediated deposition of osteochondrogenic matrix governed by hypoxia and osteogenic factors synergy

Abstract

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 cells’ 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 co‐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 cell–cell crosstalk, providing a molecular framework for hypoxic control and modulation of cells’ fate toward enthesis‐like phenotypes.

Journal
Journal Of Cellular Physiology
Publisher
Wiley
ISSN
0021-9541
URL
https://doi.org/10.1002/jcp.30138
Keywords
Cell modulation, Enthesis, Hedgehog signaling, Hypoxia-inducible factors, Osteogenic supplementation
Rights
Restricted Access
Peer Reviewed
Yes
Status
published
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