Inverse Regulation of Early and Late Chondrogenic Differentiation by Oxygen Tension Provides Cues for Stem Cell-Based Cartilage Tissue Engineering

Abstract : Background/Aims: Multipotent stem/stromal cells (MSC) are considered promising for cartilage tissue engineering. However, chondrogenic differentiation of MSC can ultimately lead to the formation of hypertrophic chondrocytes responsible for the calcification of cartilage. To prevent the production of this calcified matrix at the articular site, the late hypertrophic differentiation of MSCs must be carefully controlled. Given that articular cartilage is avascular, we hypothesized that in addition to its stimulatory role in the early differentiation of chondrogenic cells, hypoxia may prevent their late hypertrophic conversion. Methods: Early and late chondrogenic differentiation were evaluated using human adipose MSC and murine ATDC5 cells cultured under either normoxic (21%O 2) or hypoxic (5%O 2) conditions. To investigate the effect of hypoxia on late chondrogenic differentiation, the transcriptional activity of hypoxia-inducible factor-1alpha (HIF-1α) and HIF-2α were evaluated using the NoShift DNA-binding assay and through modulation of their activity (chemical inhibitor, RNA interference). Results: Our data demonstrate that low oxygen tension not only stimulates the early chondrogenic commitment of two complementary models of chondrogenic cells, but also inhibits their hypertrophic differentiation. Conclusion: These results suggest that hypoxia can be used as an instrumental tool to prevent the formation of a calcified matrix in MSC-based cartilage tissue engineering.
Complete list of metadatas

Cited literature [56 references]  Display  Hide  Download

https://www.hal.inserm.fr/inserm-01847028
Contributor : Valérie Pecqueret <>
Submitted on : Monday, July 23, 2018 - 10:35:16 AM
Last modification on : Thursday, February 7, 2019 - 4:42:00 PM
Long-term archiving on : Wednesday, October 24, 2018 - 1:11:16 PM

File

document.pdf
Publication funded by an institution

Identifiers

Collections

Citation

Sophie Portron, Vincent Hivernaud, Christophe Merceron, Julie Lesoeur, Martial Masson, et al.. Inverse Regulation of Early and Late Chondrogenic Differentiation by Oxygen Tension Provides Cues for Stem Cell-Based Cartilage Tissue Engineering. Cellular Physiology and Biochemistry, Karger, 2015, 35 (3), pp.841 - 857. ⟨10.1159/000369742⟩. ⟨inserm-01847028⟩

Share

Metrics

Record views

779

Files downloads

114