PTH receptor signaling in osteocytes governs periosteal bone formation and intracortical remodeling

Autores
Rhee, Yumie; Allen, Matthew R; Condon, Keith; Lezcano, Virginia Alicia; Ronda, Ana Carolina; Galli, Carlo; Olivos, Naomi; Passeri, Giovanni; O'Brien, Charles A; Bivi, Nicoletta; Plotkin, Lilian I; Bellido, Teresita
Año de publicación
2011
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
The periosteal and endocortical surfaces of cortical bone dictate the geometry and overall mechanical properties of bone. Yet the cellular and molecular mechanisms that regulate activity on these surfaces are far from being understood. Parathyroid hormone (PTH) has profound effects in cortical bone, stimulating periosteal expansion and at the same time accelerating intracortical bone remodeling. We report herein that transgenic mice expressing a constitutive active PTH receptor in osteocytes (DMP1-caPTHR1 mice) exhibit increased cortical bone area and an elevated rate of periosteal and endocortical bone formation. In addition, DMP1-caPTHR1 mice display a marked increase in intracortical remodeling and cortical porosity. Crossing DMP1-caPTHR1 mice with mice lacking the Wnt coreceptor, LDL-related receptor 5 (LRP5), or with mice overexpressing the Wnt antagonist Sost in osteocytes (DMP1-Sost mice) reduced or abolished, respectively, the increased cortical bone area, periosteal bone formation rate, and expression of osteoblast markers and Wnt target genes exhibited by the DMP1-caPTHR1 mice. In addition, DMP1-caPTHR1 lacking LRP5 or double transgenic DMP1-caPTHR1;DMP1-Sost mice exhibit exacerbated intracortical remodeling and increased osteoclast numbers, and markedly decreased expression of the RANK decoy receptor osteoprotegerin. Thus, whereas Sost downregulation and the consequent Wnt activation is required for the stimulatory effect of PTH receptor signaling on periosteal bone formation, the Wnt-independent increase in osteoclastogenesis induced by PTH receptor activation in osteocytes overrides the effect on Sost. These findings demonstrate that PTH receptor signaling influences cortical bone through actions on osteocytes and defines the role of Wnt signaling in PTH receptor action. © 2011 American Society for Bone and Mineral Research.
Fil: Rhee, Yumie. Indiana University School of Medicine; Estados Unidos
Fil: Allen, Matthew R. Indiana University School of Medicine; Estados Unidos
Fil: Condon, Keith. Indiana University School of Medicine; Estados Unidos
Fil: Lezcano, Virginia Alicia. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Indiana University School of Medicine; Estados Unidos
Fil: Ronda, Ana Carolina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Indiana University School of Medicine; Estados Unidos
Fil: Galli, Carlo. Indiana University School of Medicine; Estados Unidos
Fil: Olivos, Naomi. Indiana University School of Medicine; Estados Unidos
Fil: Passeri, Giovanni. Indiana University School of Medicine; Estados Unidos
Fil: O'Brien, Charles A. University of Arkansas for Medical Sciences; Estados Unidos
Fil: Bivi, Nicoletta. Indiana University School of Medicine; Estados Unidos
Fil: Plotkin, Lilian I. Indiana University School of Medicine; Estados Unidos
Fil: Bellido, Teresita. Indiana University School of Medicine; Estados Unidos. Indiana University School of Medicine; Estados Unidos
Materia
Intracortical Remodeling
Osteocytes
Periosteal Bone Formation
Pth Receptor
Wnt Signaling
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/66953
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/66953
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling PTH receptor signaling in osteocytes governs periosteal bone formation and intracortical remodelingRhee, YumieAllen, Matthew RCondon, KeithLezcano, Virginia AliciaRonda, Ana CarolinaGalli, CarloOlivos, NaomiPasseri, GiovanniO'Brien, Charles ABivi, NicolettaPlotkin, Lilian IBellido, TeresitaIntracortical RemodelingOsteocytesPeriosteal Bone FormationPth ReceptorWnt Signalinghttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3The periosteal and endocortical surfaces of cortical bone dictate the geometry and overall mechanical properties of bone. Yet the cellular and molecular mechanisms that regulate activity on these surfaces are far from being understood. Parathyroid hormone (PTH) has profound effects in cortical bone, stimulating periosteal expansion and at the same time accelerating intracortical bone remodeling. We report herein that transgenic mice expressing a constitutive active PTH receptor in osteocytes (DMP1-caPTHR1 mice) exhibit increased cortical bone area and an elevated rate of periosteal and endocortical bone formation. In addition, DMP1-caPTHR1 mice display a marked increase in intracortical remodeling and cortical porosity. Crossing DMP1-caPTHR1 mice with mice lacking the Wnt coreceptor, LDL-related receptor 5 (LRP5), or with mice overexpressing the Wnt antagonist Sost in osteocytes (DMP1-Sost mice) reduced or abolished, respectively, the increased cortical bone area, periosteal bone formation rate, and expression of osteoblast markers and Wnt target genes exhibited by the DMP1-caPTHR1 mice. In addition, DMP1-caPTHR1 lacking LRP5 or double transgenic DMP1-caPTHR1;DMP1-Sost mice exhibit exacerbated intracortical remodeling and increased osteoclast numbers, and markedly decreased expression of the RANK decoy receptor osteoprotegerin. Thus, whereas Sost downregulation and the consequent Wnt activation is required for the stimulatory effect of PTH receptor signaling on periosteal bone formation, the Wnt-independent increase in osteoclastogenesis induced by PTH receptor activation in osteocytes overrides the effect on Sost. These findings demonstrate that PTH receptor signaling influences cortical bone through actions on osteocytes and defines the role of Wnt signaling in PTH receptor action. © 2011 American Society for Bone and Mineral Research.Fil: Rhee, Yumie. Indiana University School of Medicine; Estados UnidosFil: Allen, Matthew R. Indiana University School of Medicine; Estados UnidosFil: Condon, Keith. Indiana University School of Medicine; Estados UnidosFil: Lezcano, Virginia Alicia. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Indiana University School of Medicine; Estados UnidosFil: Ronda, Ana Carolina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Indiana University School of Medicine; Estados UnidosFil: Galli, Carlo. Indiana University School of Medicine; Estados UnidosFil: Olivos, Naomi. Indiana University School of Medicine; Estados UnidosFil: Passeri, Giovanni. Indiana University School of Medicine; Estados UnidosFil: O'Brien, Charles A. University of Arkansas for Medical Sciences; Estados UnidosFil: Bivi, Nicoletta. Indiana University School of Medicine; Estados UnidosFil: Plotkin, Lilian I. Indiana University School of Medicine; Estados UnidosFil: Bellido, Teresita. Indiana University School of Medicine; Estados Unidos. Indiana University School of Medicine; Estados UnidosAmerican Society for Bone and Mineral Research2011-05info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/66953Rhee, Yumie; Allen, Matthew R; Condon, Keith; Lezcano, Virginia Alicia; Ronda, Ana Carolina; et al.; PTH receptor signaling in osteocytes governs periosteal bone formation and intracortical remodeling; American Society for Bone and Mineral Research; Journal of Bone and Mineral Research; 26; 5; 5-2011; 1035-10460884-0431CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1002/jbmr.304info:eu-repo/semantics/altIdentifier/url/https://onlinelibrary.wiley.com/doi/full/10.1002/jbmr.304info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-22T12:11:17Zoai:ri.conicet.gov.ar:11336/66953instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-10-22 12:11:18.038CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv PTH receptor signaling in osteocytes governs periosteal bone formation and intracortical remodeling
title PTH receptor signaling in osteocytes governs periosteal bone formation and intracortical remodeling
spellingShingle PTH receptor signaling in osteocytes governs periosteal bone formation and intracortical remodeling
Rhee, Yumie
Intracortical Remodeling
Osteocytes
Periosteal Bone Formation
Pth Receptor
Wnt Signaling
title_short PTH receptor signaling in osteocytes governs periosteal bone formation and intracortical remodeling
title_full PTH receptor signaling in osteocytes governs periosteal bone formation and intracortical remodeling
title_fullStr PTH receptor signaling in osteocytes governs periosteal bone formation and intracortical remodeling
title_full_unstemmed PTH receptor signaling in osteocytes governs periosteal bone formation and intracortical remodeling
title_sort PTH receptor signaling in osteocytes governs periosteal bone formation and intracortical remodeling
dc.creator.none.fl_str_mv Rhee, Yumie
Allen, Matthew R
Condon, Keith
Lezcano, Virginia Alicia
Ronda, Ana Carolina
Galli, Carlo
Olivos, Naomi
Passeri, Giovanni
O'Brien, Charles A
Bivi, Nicoletta
Plotkin, Lilian I
Bellido, Teresita
author Rhee, Yumie
author_facet Rhee, Yumie
Allen, Matthew R
Condon, Keith
Lezcano, Virginia Alicia
Ronda, Ana Carolina
Galli, Carlo
Olivos, Naomi
Passeri, Giovanni
O'Brien, Charles A
Bivi, Nicoletta
Plotkin, Lilian I
Bellido, Teresita
author_role author
author2 Allen, Matthew R
Condon, Keith
Lezcano, Virginia Alicia
Ronda, Ana Carolina
Galli, Carlo
Olivos, Naomi
Passeri, Giovanni
O'Brien, Charles A
Bivi, Nicoletta
Plotkin, Lilian I
Bellido, Teresita
author2_role author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Intracortical Remodeling
Osteocytes
Periosteal Bone Formation
Pth Receptor
Wnt Signaling
topic Intracortical Remodeling
Osteocytes
Periosteal Bone Formation
Pth Receptor
Wnt Signaling
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv The periosteal and endocortical surfaces of cortical bone dictate the geometry and overall mechanical properties of bone. Yet the cellular and molecular mechanisms that regulate activity on these surfaces are far from being understood. Parathyroid hormone (PTH) has profound effects in cortical bone, stimulating periosteal expansion and at the same time accelerating intracortical bone remodeling. We report herein that transgenic mice expressing a constitutive active PTH receptor in osteocytes (DMP1-caPTHR1 mice) exhibit increased cortical bone area and an elevated rate of periosteal and endocortical bone formation. In addition, DMP1-caPTHR1 mice display a marked increase in intracortical remodeling and cortical porosity. Crossing DMP1-caPTHR1 mice with mice lacking the Wnt coreceptor, LDL-related receptor 5 (LRP5), or with mice overexpressing the Wnt antagonist Sost in osteocytes (DMP1-Sost mice) reduced or abolished, respectively, the increased cortical bone area, periosteal bone formation rate, and expression of osteoblast markers and Wnt target genes exhibited by the DMP1-caPTHR1 mice. In addition, DMP1-caPTHR1 lacking LRP5 or double transgenic DMP1-caPTHR1;DMP1-Sost mice exhibit exacerbated intracortical remodeling and increased osteoclast numbers, and markedly decreased expression of the RANK decoy receptor osteoprotegerin. Thus, whereas Sost downregulation and the consequent Wnt activation is required for the stimulatory effect of PTH receptor signaling on periosteal bone formation, the Wnt-independent increase in osteoclastogenesis induced by PTH receptor activation in osteocytes overrides the effect on Sost. These findings demonstrate that PTH receptor signaling influences cortical bone through actions on osteocytes and defines the role of Wnt signaling in PTH receptor action. © 2011 American Society for Bone and Mineral Research.
Fil: Rhee, Yumie. Indiana University School of Medicine; Estados Unidos
Fil: Allen, Matthew R. Indiana University School of Medicine; Estados Unidos
Fil: Condon, Keith. Indiana University School of Medicine; Estados Unidos
Fil: Lezcano, Virginia Alicia. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Indiana University School of Medicine; Estados Unidos
Fil: Ronda, Ana Carolina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Indiana University School of Medicine; Estados Unidos
Fil: Galli, Carlo. Indiana University School of Medicine; Estados Unidos
Fil: Olivos, Naomi. Indiana University School of Medicine; Estados Unidos
Fil: Passeri, Giovanni. Indiana University School of Medicine; Estados Unidos
Fil: O'Brien, Charles A. University of Arkansas for Medical Sciences; Estados Unidos
Fil: Bivi, Nicoletta. Indiana University School of Medicine; Estados Unidos
Fil: Plotkin, Lilian I. Indiana University School of Medicine; Estados Unidos
Fil: Bellido, Teresita. Indiana University School of Medicine; Estados Unidos. Indiana University School of Medicine; Estados Unidos
description The periosteal and endocortical surfaces of cortical bone dictate the geometry and overall mechanical properties of bone. Yet the cellular and molecular mechanisms that regulate activity on these surfaces are far from being understood. Parathyroid hormone (PTH) has profound effects in cortical bone, stimulating periosteal expansion and at the same time accelerating intracortical bone remodeling. We report herein that transgenic mice expressing a constitutive active PTH receptor in osteocytes (DMP1-caPTHR1 mice) exhibit increased cortical bone area and an elevated rate of periosteal and endocortical bone formation. In addition, DMP1-caPTHR1 mice display a marked increase in intracortical remodeling and cortical porosity. Crossing DMP1-caPTHR1 mice with mice lacking the Wnt coreceptor, LDL-related receptor 5 (LRP5), or with mice overexpressing the Wnt antagonist Sost in osteocytes (DMP1-Sost mice) reduced or abolished, respectively, the increased cortical bone area, periosteal bone formation rate, and expression of osteoblast markers and Wnt target genes exhibited by the DMP1-caPTHR1 mice. In addition, DMP1-caPTHR1 lacking LRP5 or double transgenic DMP1-caPTHR1;DMP1-Sost mice exhibit exacerbated intracortical remodeling and increased osteoclast numbers, and markedly decreased expression of the RANK decoy receptor osteoprotegerin. Thus, whereas Sost downregulation and the consequent Wnt activation is required for the stimulatory effect of PTH receptor signaling on periosteal bone formation, the Wnt-independent increase in osteoclastogenesis induced by PTH receptor activation in osteocytes overrides the effect on Sost. These findings demonstrate that PTH receptor signaling influences cortical bone through actions on osteocytes and defines the role of Wnt signaling in PTH receptor action. © 2011 American Society for Bone and Mineral Research.
publishDate 2011
dc.date.none.fl_str_mv 2011-05
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/66953
Rhee, Yumie; Allen, Matthew R; Condon, Keith; Lezcano, Virginia Alicia; Ronda, Ana Carolina; et al.; PTH receptor signaling in osteocytes governs periosteal bone formation and intracortical remodeling; American Society for Bone and Mineral Research; Journal of Bone and Mineral Research; 26; 5; 5-2011; 1035-1046
0884-0431
CONICET Digital
CONICET
url http://hdl.handle.net/11336/66953
identifier_str_mv Rhee, Yumie; Allen, Matthew R; Condon, Keith; Lezcano, Virginia Alicia; Ronda, Ana Carolina; et al.; PTH receptor signaling in osteocytes governs periosteal bone formation and intracortical remodeling; American Society for Bone and Mineral Research; Journal of Bone and Mineral Research; 26; 5; 5-2011; 1035-1046
0884-0431
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1002/jbmr.304
info:eu-repo/semantics/altIdentifier/url/https://onlinelibrary.wiley.com/doi/full/10.1002/jbmr.304
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv American Society for Bone and Mineral Research
publisher.none.fl_str_mv American Society for Bone and Mineral Research
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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score 12.982451

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