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 vasculcar 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.
Prof. Massimo Bottini, Univ. Roma Tor Vergata, Italy
Prof. Pietro Ciancaglini and Prof. Ana Paula Ramos, Univ. Sao Paulo, Ribeirao Preto, SP Brazil
Prof. Agnieszka Strzelecka-Kiliszek, and Prof. Slawomir Pikula, Nencki Institute, Warsaw, Poland
Prof. José Luis Millán, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, USA
Veschi EA, Bolean M, Strzelecka-Kiliszek A, Bandorowicz-Pikula J, Pikula S, Granjon T, Mebarek S, Magne D, Ramos AP, Rosato N, Millán JL, Buchet R, Bottini M, Ciancaglini P. Localization of Annexin A6 in Matrix Vesicles During Physiological Mineralization. Int J Mol Sci. 2020 Feb 18;21(4):1367.
Borel M, Lollo G, Magne D, Buchet R, Brizuela L, Mebarek S. Prostate cancer-derived exosomes promote osteoblast differentiation and activity through phospholipase D2. Biochim Biophys Acta Mol Basis Dis. 2020 Dec 1;1866(12):165919.
Plaut JS, Strzelecka-Kiliszek A, Bozycki L, Pikula S, Buchet R, Mebarek S, Chadli M, Bolean M, Simao AMS, Ciancaglini P, Magrini A, Rosato N, Magne D, Girard-Egrot A, Farquharson C, Esener SC, Millan JL, Bottini M. Quantitative atomic force microscopy provides new insight into matrix vesicle mineralization Arch Biochem Biophys. 2019 May 30;667:14-21.
Bottini M, Mebarek S, Anderson KL, Strzelecka-Kiliszek A, Bozycki L, Simão AMS, Bolean M, Ciancaglini P, Pikula JB, Pikula S, Magne D, Volkmann N, Hanein D, Millán JL, Buchet R. Matrix vesicles from chondrocytes and osteoblasts: their biogenesis, properties, functions and biomimetic models. Biochim Biophys Acta Gen Subj. 2018 Mar;1862(3):532-546.