Degeneration and plasticity of the locomotor system

RESEARCHERS
LEFEBVRE Suzie
CORVOL Maité
LECTURERS-RESEARCHERS
BIONDI Olivier
BORDERIE Didier
CHANOINE Christophe
CHARBONNIER Frédéric
DELLA GASPERA Bruno
LOPES Philippe
NGUYEN Christelle
RANNOU François
WEILL Laure
TECHNICAL STAFF
DELERS Perrine
ETIENNE François
SAPALY Delphine
TAHIRI Khadija
PhD STUDENTS
AKOUM Joulnar
BEZIER Cynthia
D’AMICO Domenico
EL KHOURY Mirella

Our research team aims at understanding the basic mechanisms involved in structure and functioning of the healthy and pathological locomotor system. The team gathers clinicians and researchers, who are experts in cellular and molecular biology, biochemistry, exercise physiology and locomotor diseases, aiming to develop new therapeutic strategies. We will pay particular attention to cellular and functional relationships between the different cell types of 1) the motor unit, i.e. motor neurons, glial cells and muscle fibers and of 2) the osteoarticular system i.e. chondrocytes and synoviocytes, in normal and pathological conditions. The unique expertise and competencies developed within the team allow us to address these issues in conditions of modulated muscular activity, physical exercise and mechanical cell stress. Our project is divided into four work packages (WP), each one headed by a PI (F. Rannou, O. Biondi, L. Weill, and S. Lefebvre) whereby the complementary competencies of all the team’s researchers are shared. WP1 will deal with the development and plasticity of the normal and pathological locomotor system, WP2 will analyze the interplay between energetic metabolism, oxidative stress and inflammation in the locomotor diseases, WP3 will investigate the role of RNA metabolism in neuromuscular pathologies, and WP4 deals with the nuclear signaling pathways in RNA metabolism, cellular differentiation and diseases. The studies will be conducted in direct connection with both the physical medicine and rehabilitation and the automatized biological diagnostic departments from the Cochin hospital to foster translational activities.

Panel presenting the different components of the mouse motor unit at 12 days of age: 3D-reconstruction of the sensory v-GLUT2-positive synapses on a lumbar motorneuron (left), neuromuscular junction labeled with neurofilament ligth-chain (pre-synaptic) and a-bungarotoxin (post-synaptic), and type I myosin heavy chain-positive myofibers on a DIC cross-section image of soleus muscle. (Scales bar: 10µm, middle, and 100µm, right).

Histology of a knee joint from one week C57BL/6 mice. Safranin O/Fast green coloration (magnification 10×). Safranin-o is a marker of cartilage matrix Proteoglycans , Fast green counterstains non specific collagen proteins M : meniscus, RC: Resting chondrocytes , PC: Proliferating Chondrocytes , HC: Hypertrophic Chondrocytes, OsC: Ossification center.
MAIN PUBLICATIONS
Musashi 1 regulates the timing and extent of meiotic mRNA translational activation by promoting the use of specific CPEs.
Weill L, Belloc E, Castellazzi CL, Méndez R.
Nat Struct Mol Biol. 2017 Aug;24(8):672-681
Intradiscal Glucocorticoid Injection for Patients With Chronic Low Back Pain Associated With Active Discopathy: A Randomized Trial.
Nguyen C, Boutron I, Baron G, Sanchez K, Palazzo C, Benchimol R, Paris G, James-Belin É, Lefèvre-Colau MM, Beaudreuil J, Laredo JD, Béra-Louville A, Cotton A, Drapé JL, Feydy A, Ravaud P, Rannou F, Poiraudeau S.
Ann Intern Med. 2017 Apr 18;166(8):547-556
IGF-1R Reduction Triggers Neuroprotective Signaling Pathways in Spinal Muscular Atrophy Mice.
Biondi O, Branchu J, Ben Salah A, Houdebine L, Bertin L, Chali F, Desseille C, Weill L, Sanchez G, Lancelin C, Aïd S, Lopes P, Pariset C, Lécolle S, Côté J, Holzenberger M, Chanoine C, Massaad C, Charbonnier F.
J Neurosci. 2015 Aug 26;35(34):12063-79
Small-molecule flunarizine increases SMN protein in nuclear Cajal bodies and motor function in a mouse model of spinal muscular atrophy.
Sapaly D, Dos Santos M, Delers P, Biondi O, Quérol G, Houdebine L, Khoobarry K, Girardet F, Burlet P, Armand AS, Chanoine C, Bureau JF, Charbonnier F, Lefebvre S.
Sci Rep. 2018 Feb 1;8(1):2075
Use of Resveratrol Self-Emulsifying Systems in T/C28a2 Cell Line as Beneficial Effectors in Cellular Uptake and Protection Against Oxidative Stress-Mediated Death.
Le Clanche S, Cheminel T, Rannou F, Bonnefont-Rousselot D, Borderie D, Charrueau C.
Front Pharmacol. 2018 May 24;9:538