Comparative transcriptomics reveals RhoE as a novel regulator of actin dynamics in bone-resorbing osteoclasts

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dc.contributor.author Georgess, Dan
dc.contributor.author Mazzorana, Marlene
dc.contributor.author Terrado, Jose
dc.contributor.author Delpart, Chrisitne
dc.contributor.author Chamot, Christophe
dc.contributor.author Guasch, Rosa M.
dc.contributor.author Perez-Roger, Ignocia
dc.contributor.author Jurdic, Pierre
dc.contributor.author Machuca-Gayet, Irma
dc.date.accessioned 2019-04-04T10:02:55Z
dc.date.available 2019-04-04T10:02:55Z
dc.date.copyright 2014 en_US
dc.date.issued 2019-04-04
dc.identifier.issn 1939-4586 en_US
dc.identifier.uri http://hdl.handle.net/10725/10338
dc.description.abstract The function of osteoclasts (OCs), multinucleated giant cells (MGCs) of the monocytic lineage, is bone resorption. To resorb bone, OCs form podosomes. These are actin-rich adhesive structures that pattern into rings that drive OC migration and into “sealing-zones” (SZs) that confine the resorption lacuna. Although changes in actin dynamics during podosome patterning have been documented, the mechanisms that regulate these changes are largely unknown. From human monocytic precursors, we differentiated MGCs that express OC degradation enzymes but are unable to resorb the mineral matrix. We demonstrated that, despite exhibiting bona fide podosomes, these cells presented dysfunctional SZs. We then performed two-step differential transcriptomic profiling of bone-resorbing OCs versus nonresorbing MGCs to generate a list of genes implicated in bone resorption. From this list of candidate genes, we investigated the role of Rho/Rnd3. Using primary RhoE-deficient OCs, we demonstrated that RhoE is indispensable for OC migration and bone resorption by maintaining fast actin turnover in podosomes. We further showed that RhoE activates podosome component cofilin by inhibiting its Rock-mediated phosphorylation. We conclude that the RhoE-Rock-cofilin pathway, by promoting podosome dynamics and patterning, is central for OC migration, SZ formation, and, ultimately, bone resorption. en_US
dc.language.iso en en_US
dc.title Comparative transcriptomics reveals RhoE as a novel regulator of actin dynamics in bone-resorbing osteoclasts en_US
dc.type Article en_US
dc.description.version Published en_US
dc.author.school SAS en_US
dc.author.idnumber 201900498 en_US
dc.author.department Natural Sciences en_US
dc.description.embargo N/A en_US
dc.relation.journal Molecular Biology of the Cell en_US
dc.journal.volume 25 en_US
dc.journal.issue 3 en_US
dc.article.pages 319-426 en_US
dc.identifier.doi https://doi.org/10.1091/mbc.e13-07-0363 en_US
dc.identifier.ctation Georgess, D., Mazzorana, M., Terrado, J., Delprat, C., Chamot, C., Guasch, R. M., ... & Machuca-Gayet, I. (2014). Comparative transcriptomics reveals RhoE as a novel regulator of actin dynamics in bone-resorbing osteoclasts. Molecular biology of the cell, 25(3), 380-396. en_US
dc.author.email dan.georgess@lau.edu.lb en_US
dc.identifier.tou http://libraries.lau.edu.lb/research/laur/terms-of-use/articles.php en_US
dc.identifier.url https://www.molbiolcell.org/doi/full/10.1091/mbc.e13-07-0363 en_US
dc.author.affiliation Lebanese American University en_US

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