Dev108654 1..14

نویسندگان

  • Emmanuelle Havis
  • Marie-Ange Bonnin
  • Isabel Olivera-Martinez
  • Nicolas Nazaret
  • Mathilde Ruggiu
  • Jennifer Weibel
  • Charles Durand
  • Marie-Justine Guerquin
  • Christelle Bonod-Bidaud
  • Florence Ruggiero
  • Ronen Schweitzer
  • Delphine Duprez
چکیده

The molecular signals driving tendon development are not fully identified. We have undertaken a transcriptome analysis of mouse limb tendon cells that were isolated at different stages of development based on scleraxis (Scx) expression. Microarray comparisons allowed us to establish a list of genes regulated in tendon cells during mouse limb development. Bioinformatics analysis of the tendon transcriptome showed that the two most strongly modified signalling pathways were TGF-β andMAPK. TGF-β/SMAD2/3 gainand loss-offunction experiments in mouse limb explants and mesenchymal stem cells showed that TGF-β signalling was sufficient and required via SMAD2/3 to drive mouse mesodermal stem cells towards the tendon lineage ex vivo and in vitro. TGF-β was also sufficient for tendon gene expression in late limb explants during tendon differentiation. FGF does not have a tenogenic effect and the inhibition of the ERK MAPK signalling pathway was sufficient to activate Scx in mouse limb mesodermal progenitors and mesenchymal stem cells.

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تاریخ انتشار 2014