Analysis of post transcriptional regulation of SOX9 mRNA during in vitro chondrogenesis.

Abstract

Marker genes are used to monitor chondrogenic differentiation, but little is known about the turnover of their mRNA during this process. We set out to measure the half life of mRNA encoding the transcription factor SOX9, an important marker of chondrocytic phenotype. We dedifferentiated human articular chondrocytes in monolayer culture before placing them in chondrogenic three-dimensional pellet cultures. At the same time, we induced chondrocytic differentiation of human bone marrow-derived mesenchymal stem cells under the same three-dimensional conditions. Pellets were cultured in standard chondrogenic media with and without BMP7. We found that SOX9 mRNA half life exhibited an inverse correlation with total SOX9 mRNA levels in both dedifferentiating human articular chondrocytes and chondrogenic pellet cultures. There was no evidence for a specific effect of BMP7 on SOX9 mRNA decay. Our findings provide an insight into a level of gene control rarely explored in regenerative medicine, which could be important in the optimization of in vitro cartilage production.