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ANR-DFG 2019: Deciphering the biophysical basis by which Glycosaminoglycans CONtrol growth factor signaling during development: a biomimetic approach (GlyCON)

Published on 27 November 2019
Dr. Elisa Migliorini
CNRS researcher at BRM
Prof. Andrea Vortkamp
Director of the Developmental biology department
University of Duisburg- Essen
Expert in surface chemistry applied to biotechnology
Expert in pre and postnatal bone development Interest in the role of HS during endochondral ossification related to Indian Hedgehog signalling


Dr. Romain Vivès
CNRS director
Group leader of the SAGAG group at IBS
Expert in glycobiology and on structural characterization of GAGs

The project
During development glycosoaminoglycans (GAG), especially heparan sulfate (HS), act as critical regulators of growth factor signaling like that of bone morphogenetic proteins (BMPs) and Indian hedgehog (Ihh), both regulators of skeletal development. The exact mechanisms by which HS controls signal presentation, distribution and activation are not well understood. Recent studies indicate the existence of a HS sulfation code that is recognized by distinct surface domains of proteins. Besides binding to HS some growth factors also bind to the GAG Chondroitin sulfate (CS), but with lower affinity. In this project we aim to decipher the specificities of growth factor–GAG interaction using biomimetic platforms presenting immobilized GAGs. These platforms permit to control the relative surface concentration and binding affinities between growth factors and GAGs. The impact of the binding modalities will be tested in in biological systems including cell culture and tissues of mouse mutants. 

WP1: Investigate the HS structure which determines different affinities for GFs in vitro and in vivo on mice mutant
WP2: understand how the relative composition of HS and CS impacts on the bioactivity of growth factors signaling in vitro and in vivo?

People involved in the project

Fatima Asar
PhD student at DUE
Jean Le Pennec
PhD student at CEA
Julius Sefkow-Werner
PhD student at CEA
Evelyne Gout
Engineer at IBS


Learning from BMPs and their biophysical extracellular matrix microenvironment for biomaterial design
Elisa Migliorini, Amaris Guevara-Garcia, Corinne Albiges-Rizo, Catherine Picart
BONE, Elsevier, 2020, 141, pp.115540. ⟨10.1016/j.bone.2020.115540

Heparan sulfate co-immobilized with cRGD ligands and BMP2 on biomimetic platforms promotes BMP2-mediated osteogenic differentiation
Julius Sefkow-Werner, Paul Machillot, Adrià Sales, Elaine Castro-Ramirez, Melissa Degardin, Didier Boturyn, Elisabetta Ada Cavalcanti-Adam, Corinne Albiges-Rizo, Catherine Picart, Elisa Migliorini
Acta Biomaterialia, Elsevier, 2020, 114, pp.90-103. ⟨10.1016/j.actbio.2020.07.015

Chondrocytes respond to an altered heparan sulfate composition with distinct changes of heparan sulfate structure and increased levels of chondroitin sulfate
Velina Bachvarova, Tabea Dierker , Jeffrey Esko  Daniel Hoffmann , Lena Kjellen , Andrea Vortkamp.
Matrix Biology 2020, 20;S0945-053X(20)30029-9. (10.1016/j.matbio.2020.03.006)

An altered heparan sulfate structure in the articular cartilage protects against osteoarthritis
A.-C. Severmann, K. Jochmann , K. Feller, V. Bachvarova, V. Piombo, R. Stange, T. Holzer, B. Brachvogel, J. Esko, T. Pap, D. Hoffmann, A. Vortkamp
Osteoarthritis and Cartilage 28 (2020) 977e987 (10.1016/j.joca.2020.04.002)