Valérie Cormier-Daire et Laurence Legeai-Mallet

Molecular and Physiopathological bases of osteochondrodysplasia

Valérie Cormier-Daire  et Laurence Legeai-Mallet
  • Carine Le Goff
  • Céline Huber
  • Nabil Kaci
  • Catherine Benoist-Lasselin
  • Quentin Siour
  • Martin Biosse Duplan
  • Davide Komla Ebri
  • Mathilde Doyard
  • Maxence Cornille
  • Laure Delhon
  • Muriel de La Dure-Molla
  • Ludovic Martin
  • Emilie Damboise
  • Johanne Dubail
  • Geneviève Baujat
  • Caroline Michot
  • Kim-Hanh Le Quan Sang
  • Stéphanie Pannier
  • Zagorka Péjin

Molecular and Physiopathological bases of osteochondrodysplasia

Genetic disorders of the skeletal system may affect bone and/or cartilage formation from early embryo-fetal development up to childhood. Skeletal development is a temporally-regulated non-linear process orchestrated by a complex genetic network that proceeds via two distinct ossification mechanisms, namely membranous and endochondral. An impairment of this process is responsible for a group of rare and often severe disorders: the osteochondrodysplasia.

Our research aims to contribute to the understanding of the ossification process by:

1. Identifying the molecular basis of osteochondrodyplasias, studying large cohort of patients clinically well characterized through the reference center for skeletal dysplasia.

2. Developing novel therapeutic approaches in bone fragility disorders using human osteoblasts and mouse models.

3. Deciphering proteoglycan synthesis impairment, in chondrodysplasia with multiple dislocations, using cellular and zebrafish models.

4. Understanding the role of ADAMTS(L) proteins and SMAD4 in TGFb signaling, involved in the acromelic dysplasia group, using cellular and mouse models and testing the efficiency of TGFb neutralizing antibodies to counteract enhanced TGFb signaling.

5. Elucidating the molecular mechanisms involved in endochondral and membranous ossification in FGFR3-related osteochondrodysplasias during growth using several conditional knock-in fgfr3 mouse models and understanding the role of fgfr family in craniofacial development.

6. Developing pharmacological approaches to counteract FGFR3 activating mutations by testing peptides, tyrosine kinase inhibitors, antibodies using in human cellular models, ex-vivo cultures (long bone, mandible and calvaria) and in vivo experiments.