BMP-2, hypoxia, and COL1A1/HtrA1 siRNAs favor neo-cartilage hyaline matrix formation in chondrocytes

David Ollitrault, Florence Legendre, Carole Drougard, Mélanie Briand, Hervé Benateau, Didier Goux, Hanane Chajra, Laurent Poulain, Daniel Hartmann, Denis Vivien, Vijayalakshmi Shridhar, Alfonso Baldi, Frédéric Mallein-Gerin, Karim Boumediene, Magali Demoor, Philippe Galera

Research output: Contribution to journalArticle

19 Scopus citations

Abstract

Osteoarthritis (OA) is an irreversible pathology that causes a decrease in articular cartilage thickness, leading finally to the complete degradation of the affected joint. The low spontaneous repair capacity of cartilage prevents any restoration of the joint surface, making OA a major public health issue. Here, we developed an innovative combination of treatment conditions to improve the human chondrocyte phenotype before autologous chondrocyte implantation. First, we seeded human dedifferentiated chondrocytes into a collagen sponge as a scaffold, cultured them in hypoxia in the presence of a bone morphogenetic protein (BMP), BMP-2, and transfected them with small interfering RNAs targeting two markers overexpressed in OA dedifferentiated chondrocytes, that is, type I collagen and/or HtrA1 serine protease. This strategy significantly decreased mRNA and protein expression of type I collagen and HtrA1, and led to an improvement in the chondrocyte phenotype index of differentiation. The effectiveness of our in vitro culture process was also demonstrated in the nude mouse model in vivo after subcutaneous implantation. We, thus, provide here a new protocol able to favor human hyaline chondrocyte phenotype in primarily dedifferentiated cells, both in vitro and in vivo. Our study also offers an innovative strategy for chondrocyte redifferentiation and opens new opportunities for developing therapeutic targets.

Original languageEnglish (US)
Pages (from-to)133-147
Number of pages15
JournalTissue Engineering - Part C: Methods
Volume21
Issue number2
DOIs
StatePublished - Feb 1 2015

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ASJC Scopus subject areas

  • Bioengineering
  • Medicine (miscellaneous)
  • Biomedical Engineering

Cite this

Ollitrault, D., Legendre, F., Drougard, C., Briand, M., Benateau, H., Goux, D., Chajra, H., Poulain, L., Hartmann, D., Vivien, D., Shridhar, V., Baldi, A., Mallein-Gerin, F., Boumediene, K., Demoor, M., & Galera, P. (2015). BMP-2, hypoxia, and COL1A1/HtrA1 siRNAs favor neo-cartilage hyaline matrix formation in chondrocytes. Tissue Engineering - Part C: Methods, 21(2), 133-147. https://doi.org/10.1089/ten.tec.2013.0724