The MEM2 team (Metabolism, Enzymes and Molecular Mechanisms) is located in the Lyon-Tech La Doua campus, in the Raulin building.
At the physiological level, the team is particularly intestered in the molecular and cellular mechanisms involved in the initiation of tissue mineralization, and in particular in the involvement of the so-called matrix vesicles that are released by hypertrophic chondrocytes and osteoblasts. At the pathological level, the team explores the mechanisms responsible for vascular calcification in atherosclerosis, type 2 diabetes and chronic kidney disease, and those involved in enthesis ossification in spondyloarthritis. Additionnally, MEM2 is also involved in the study of the onset and the development of prostate cancer-associated bone metastasis which is osteogenic.
Extracellular vesicles (EVs) are lipid bilayer-enclosed nanosized particles released by cells during physiological as well as pathological processes. In the MEM2 team, we are studying for long the involvement of EVs in tissue mineralization. In physiological conditions, hypertrophic chondrocytes release a special class of EVs, named matrix vesicles (MVs), to initiate bone mineralization. We are exploring the mechanisms of MV release, and how MVs initiate crystal nucleation and growth. In pathological conditions, and in particular in disorders associated with vascular calcification (atherosclerosis, chronic kidney disease, type 2 diabetes) vascular smooth muscle cells and macrophages appear to release calcifying EVs. One of the main functions of EVs is to act as signalosomes in cell-cell communication in a pleiotropic manner. This task is mostly performed by a specific class of EVs, named exosomes. Whether calcifying EVs serve, like exosomes, as cellular communication structures is under investigation. MVs are released from the apical side of plasma membranes of mineralizing cells, and harbors the whole machinery necessary to initiate apatite nucleation in their lumen. We are also interested in the role of exosomes in the dialog between prostate cancer cells and bone metastasis microenvironment, notably with the osteoblasts, and in the participation of the hydrolase phospholipase D in this process.
Vascular calcification is a pathological but relatively common life-threatening event, associated with atherosclerosis, type 2 diabetes and chronic kidney disease. In these diseases, vascular smooth muscle cells contribute to calcification but the molecular mechanisms involved in calcification remain obscure. Moreover, the impact of calcification, particularly in atherosclerotic plaques, remains controversial. Our projects aim to better understand how arteries calcify, and determine the beneficial and/or harmful impact of different types of vascular calcification. We have an interest in determining the involvement of tissue-nonspecific alkaline phosphatase (TNAP), the only necessary enzyme in bone mineralization, in vascular calcification and whether TNAP inhibition protects from calcification and mortality in a model of atherosclerosis. We are also interested in the role of sphingolipid metabolism, specially sphingosine 1-phosphate, in chronic kidney disease-related vascular calcification.
Spondyloarthritis (SpA) is a common rheumatic disease that causes considerable disability, due to pain and structural alterations. In particular, there is abnormal ossification in the entheses, leading to ankylosis of this zone where tendons are inserted into bone. We focus on the cellular and molecular mechanisms of bone formation in arthritic enthesis. Better defining the relative contribution of mechanical stress, inflammation, and soluble factors should help understand SpA pathophysiology. We investigate in particular the role of some molecular targets that are deregulated in SpA-like conditions, such as the BMP pathway and the sphingolipid metabolism.
Carolina Chieffo, Emiliano Altamura, Guillaume Pilet, Saïda Mebarek, Peter Strazewski and Michele Fiore*
Daverio, Z., Balcerczyk, A., Rautureau, G.J.P., Panthu, B.
Heitor Gobbi Sebinelli, Luiz Henrique Silva Andrilli, Bruno Zoccaratto Favarin, Marcos Aantonio Eufrasio Cruz, Maytê Bolean, Michele Fiore, Carolina Chieffo, David Magne, Andrea Magrini, Ana Paula Ramos, José Luis Millán, Saida Mebarek, Rene Buchet, Massimo Bottini and Pietro Ciancaglini
Carolina Chieffo, Emiliano Altamura, Layth Ben Trad, Guillaume Pilet, Ofelia Maniti, Thierry Granjon, Saïda Mebarek, Peter Strazewski, Michele Fiore*
Bessueille L, Kawtharany L, Quillard T, Goettsch C, Briolay A, Taraconat N, Balayssac S, Gilard V, Mebarek S, Peyruchaud O, Duboeuf F, Bouillot C, Pinkerton A, Mechtouff L Buchet R, Hamade E, Zibara K, Fonta C, Canet-Soulas E, Millan JL, Magne D