Comparative transcriptomics reveals RhoE as a novel regulator of actin dynamics in bone-resorbing osteoclasts
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 l...
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2014
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| Online Access: | http://hdl.handle.net/10725/10338 https://doi.org/10.1091/mbc.e13-07-0363 http://libraries.lau.edu.lb/research/laur/terms-of-use/articles.php https://www.molbiolcell.org/doi/full/10.1091/mbc.e13-07-0363 |
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| _version_ | 1864513486551252992 |
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| author | Georgess, Dan |
| author2 | Mazzorana, Marlene Terrado, Jose Delpart, Chrisitne Chamot, Christophe Guasch, Rosa M. Perez-Roger, Ignocia Jurdic, Pierre Machuca-Gayet, Irma |
| author2_role | author author author author author author author author |
| author_facet | Georgess, Dan Mazzorana, Marlene Terrado, Jose Delpart, Chrisitne Chamot, Christophe Guasch, Rosa M. Perez-Roger, Ignocia Jurdic, Pierre Machuca-Gayet, Irma |
| author_role | author |
| dc.creator.none.fl_str_mv | Georgess, Dan Mazzorana, Marlene Terrado, Jose Delpart, Chrisitne Chamot, Christophe Guasch, Rosa M. Perez-Roger, Ignocia Jurdic, Pierre Machuca-Gayet, Irma |
| dc.date.none.fl_str_mv | 2014 2019-04-04T10:02:55Z 2019-04-04T10:02:55Z 2019-04-04 |
| dc.identifier.none.fl_str_mv | 1939-4586 http://hdl.handle.net/10725/10338 https://doi.org/10.1091/mbc.e13-07-0363 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. http://libraries.lau.edu.lb/research/laur/terms-of-use/articles.php https://www.molbiolcell.org/doi/full/10.1091/mbc.e13-07-0363 |
| dc.language.none.fl_str_mv | en |
| dc.relation.none.fl_str_mv | Molecular Biology of the Cell |
| dc.rights.*.fl_str_mv | info:eu-repo/semantics/openAccess |
| dc.title.none.fl_str_mv | Comparative transcriptomics reveals RhoE as a novel regulator of actin dynamics in bone-resorbing osteoclasts |
| dc.type.none.fl_str_mv | Article info:eu-repo/semantics/publishedVersion info:eu-repo/semantics/article |
| description | 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. |
| eu_rights_str_mv | openAccess |
| format | article |
| id | LAURepo_6a3bcf7203c10a0b3ecac1ec12e95abc |
| identifier_str_mv | 1939-4586 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. |
| language_invalid_str_mv | en |
| network_acronym_str | LAURepo |
| network_name_str | Lebanese American University repository |
| oai_identifier_str | oai:laur.lau.edu.lb:10725/10338 |
| publishDate | 2014 |
| repository.mail.fl_str_mv | |
| repository.name.fl_str_mv | |
| repository_id_str | |
| spelling | Comparative transcriptomics reveals RhoE as a novel regulator of actin dynamics in bone-resorbing osteoclastsGeorgess, DanMazzorana, MarleneTerrado, JoseDelpart, ChrisitneChamot, ChristopheGuasch, Rosa M.Perez-Roger, IgnociaJurdic, PierreMachuca-Gayet, IrmaThe 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.PublishedN/A2019-04-04T10:02:55Z2019-04-04T10:02:55Z20142019-04-04Articleinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/article1939-4586http://hdl.handle.net/10725/10338https://doi.org/10.1091/mbc.e13-07-0363Georgess, 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.http://libraries.lau.edu.lb/research/laur/terms-of-use/articles.phphttps://www.molbiolcell.org/doi/full/10.1091/mbc.e13-07-0363enMolecular Biology of the Cellinfo:eu-repo/semantics/openAccessoai:laur.lau.edu.lb:10725/103382021-03-19T10:45:32Z |
| spellingShingle | Comparative transcriptomics reveals RhoE as a novel regulator of actin dynamics in bone-resorbing osteoclasts Georgess, Dan |
| status_str | publishedVersion |
| title | Comparative transcriptomics reveals RhoE as a novel regulator of actin dynamics in bone-resorbing osteoclasts |
| title_full | Comparative transcriptomics reveals RhoE as a novel regulator of actin dynamics in bone-resorbing osteoclasts |
| title_fullStr | Comparative transcriptomics reveals RhoE as a novel regulator of actin dynamics in bone-resorbing osteoclasts |
| title_full_unstemmed | Comparative transcriptomics reveals RhoE as a novel regulator of actin dynamics in bone-resorbing osteoclasts |
| title_short | Comparative transcriptomics reveals RhoE as a novel regulator of actin dynamics in bone-resorbing osteoclasts |
| title_sort | Comparative transcriptomics reveals RhoE as a novel regulator of actin dynamics in bone-resorbing osteoclasts |
| url | http://hdl.handle.net/10725/10338 https://doi.org/10.1091/mbc.e13-07-0363 http://libraries.lau.edu.lb/research/laur/terms-of-use/articles.php https://www.molbiolcell.org/doi/full/10.1091/mbc.e13-07-0363 |