The p38α MAPK function in osteoprecursors is required for bone formation and bone homeostasis in adult mice

p38 MAPK activity plays an important role in several steps of the osteoblast lineage progression through activation of osteoblast-specific transcription factors and it is also essential for the acquisition of the osteoblast phenotype in early development. Although reports indicate p38 signalling pla...

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Autores: Rodríguez Carballo, Edgardo, Gamez Molina, Beatriz, Sedó Cabezón, Lara, Sánchez Feutrie, Manuela, Zorzano Olarte, Antonio, Manzanares Céspedes, María Cristina, Rosa López, José Luis, Ventura Pujol, Francesc
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2014
País:España
Institución:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repositorio:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:2445/59376
Acceso en línea:https://hdl.handle.net/2445/59376
Access Level:acceso abierto
Palabra clave:Fèmur
Ratolins (Animals de laboratori)
Homeòstasi
Creixement dels ossos
Femur
Mice (Laboratory animals)
Homeostasis
Bones growth
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spelling The p38α MAPK function in osteoprecursors is required for bone formation and bone homeostasis in adult miceRodríguez Carballo, EdgardoGamez Molina, BeatrizSedó Cabezón, LaraSánchez Feutrie, ManuelaZorzano Olarte, AntonioManzanares Céspedes, María CristinaRosa López, José LuisVentura Pujol, FrancescFèmurRatolins (Animals de laboratori)HomeòstasiCreixement dels ossosFemurMice (Laboratory animals)HomeostasisBones growthp38 MAPK activity plays an important role in several steps of the osteoblast lineage progression through activation of osteoblast-specific transcription factors and it is also essential for the acquisition of the osteoblast phenotype in early development. Although reports indicate p38 signalling plays a role in early skeletal development, its specific contributions to adult bone remodelling are still to be clarified. Methodology/Principal Findings: We evaluated osteoblast-specific deletion of p38 alpha to determine its significance in early skeletogenesis, as well as for bone homeostasis in adult skeleton. Early p38 alpha deletion resulted in defective intramembranous and endochondral ossification in both calvaria and long bones. Mutant mice showed reduction of trabecular bone volume in distal femurs, associated with low trabecular thickness. In addition, knockout mice also displayed decreased femoral cortical bone volume and thickness. Deletion of p38 alpha did not affect osteoclast function. Yet it impaired osteoblastogenesis and osteoblast maturation and activity through decreased expression of osteoblast-specific transcription factors and their targets. Furthermore, the inducible Cre system allowed us to control the onset of p38 alpha disruption after birth by removal of doxycycline. Deletion of p38 alpha at three or eight weeks postnatally led to significantly lower trabecular and cortical bone volume after 6 or 12 months. Conclusions: Our data demonstrates that, in addition to early skeletogenesis, p38 alpha is essential for osteoblasts to maintain their function in mineralized adult bone, as bone anabolism should be sustained throughout life. Moreover, our data also emphasizes that clinical development of p38 inhibitors should take into account their potential bone effects.Public Library of Science (PLoS)2014201420142014info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersion12 p.application/pdfhttps://hdl.handle.net/2445/59376Articles publicats en revistes (Ciències Fisiològiques)reponame:Recercat. Dipósit de la Recerca de Catalunyainstname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)InglésReproducció del document publicat a: http://dx.doi.org/10.1371/journal.pone.0102032PLoS One, 2014, vol. 9, num. 7http://dx.doi.org/10.1371/journal.pone.0102032cc-by (c) Rodríguez-Carballo, E. et al., 2014http://creativecommons.org/licenses/by/3.0/esinfo:eu-repo/semantics/openAccessoai:recercat.cat:2445/593762026-05-29T05:05:01Z
dc.title.none.fl_str_mv The p38α MAPK function in osteoprecursors is required for bone formation and bone homeostasis in adult mice
title The p38α MAPK function in osteoprecursors is required for bone formation and bone homeostasis in adult mice
spellingShingle The p38α MAPK function in osteoprecursors is required for bone formation and bone homeostasis in adult mice
Rodríguez Carballo, Edgardo
Fèmur
Ratolins (Animals de laboratori)
Homeòstasi
Creixement dels ossos
Femur
Mice (Laboratory animals)
Homeostasis
Bones growth
title_short The p38α MAPK function in osteoprecursors is required for bone formation and bone homeostasis in adult mice
title_full The p38α MAPK function in osteoprecursors is required for bone formation and bone homeostasis in adult mice
title_fullStr The p38α MAPK function in osteoprecursors is required for bone formation and bone homeostasis in adult mice
title_full_unstemmed The p38α MAPK function in osteoprecursors is required for bone formation and bone homeostasis in adult mice
title_sort The p38α MAPK function in osteoprecursors is required for bone formation and bone homeostasis in adult mice
dc.creator.none.fl_str_mv Rodríguez Carballo, Edgardo
Gamez Molina, Beatriz
Sedó Cabezón, Lara
Sánchez Feutrie, Manuela
Zorzano Olarte, Antonio
Manzanares Céspedes, María Cristina
Rosa López, José Luis
Ventura Pujol, Francesc
author Rodríguez Carballo, Edgardo
author_facet Rodríguez Carballo, Edgardo
Gamez Molina, Beatriz
Sedó Cabezón, Lara
Sánchez Feutrie, Manuela
Zorzano Olarte, Antonio
Manzanares Céspedes, María Cristina
Rosa López, José Luis
Ventura Pujol, Francesc
author_role author
author2 Gamez Molina, Beatriz
Sedó Cabezón, Lara
Sánchez Feutrie, Manuela
Zorzano Olarte, Antonio
Manzanares Céspedes, María Cristina
Rosa López, José Luis
Ventura Pujol, Francesc
author2_role author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Fèmur
Ratolins (Animals de laboratori)
Homeòstasi
Creixement dels ossos
Femur
Mice (Laboratory animals)
Homeostasis
Bones growth
topic Fèmur
Ratolins (Animals de laboratori)
Homeòstasi
Creixement dels ossos
Femur
Mice (Laboratory animals)
Homeostasis
Bones growth
description p38 MAPK activity plays an important role in several steps of the osteoblast lineage progression through activation of osteoblast-specific transcription factors and it is also essential for the acquisition of the osteoblast phenotype in early development. Although reports indicate p38 signalling plays a role in early skeletal development, its specific contributions to adult bone remodelling are still to be clarified. Methodology/Principal Findings: We evaluated osteoblast-specific deletion of p38 alpha to determine its significance in early skeletogenesis, as well as for bone homeostasis in adult skeleton. Early p38 alpha deletion resulted in defective intramembranous and endochondral ossification in both calvaria and long bones. Mutant mice showed reduction of trabecular bone volume in distal femurs, associated with low trabecular thickness. In addition, knockout mice also displayed decreased femoral cortical bone volume and thickness. Deletion of p38 alpha did not affect osteoclast function. Yet it impaired osteoblastogenesis and osteoblast maturation and activity through decreased expression of osteoblast-specific transcription factors and their targets. Furthermore, the inducible Cre system allowed us to control the onset of p38 alpha disruption after birth by removal of doxycycline. Deletion of p38 alpha at three or eight weeks postnatally led to significantly lower trabecular and cortical bone volume after 6 or 12 months. Conclusions: Our data demonstrates that, in addition to early skeletogenesis, p38 alpha is essential for osteoblasts to maintain their function in mineralized adult bone, as bone anabolism should be sustained throughout life. Moreover, our data also emphasizes that clinical development of p38 inhibitors should take into account their potential bone effects.
publishDate 2014
dc.date.none.fl_str_mv 2014
2014
2014
2014
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/2445/59376
url https://hdl.handle.net/2445/59376
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Reproducció del document publicat a: http://dx.doi.org/10.1371/journal.pone.0102032
PLoS One, 2014, vol. 9, num. 7
http://dx.doi.org/10.1371/journal.pone.0102032
dc.rights.none.fl_str_mv cc-by (c) Rodríguez-Carballo, E. et al., 2014
http://creativecommons.org/licenses/by/3.0/es
info:eu-repo/semantics/openAccess
rights_invalid_str_mv cc-by (c) Rodríguez-Carballo, E. et al., 2014
http://creativecommons.org/licenses/by/3.0/es
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv 12 p.
application/pdf
dc.publisher.none.fl_str_mv Public Library of Science (PLoS)
publisher.none.fl_str_mv Public Library of Science (PLoS)
dc.source.none.fl_str_mv Articles publicats en revistes (Ciències Fisiològiques)
reponame:Recercat. Dipósit de la Recerca de Catalunya
instname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
instname_str Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
reponame_str Recercat. Dipósit de la Recerca de Catalunya
collection Recercat. Dipósit de la Recerca de Catalunya
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,811543

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