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
- Institución
- Consejo Nacional de Investigaciones Científicas y Técnicas
- OAI Identificador
- oai:ri.conicet.gov.ar:11336/66953
Ver los metadatos del registro completo
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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 Técnicas2025-09-29T10:39:03Zoai: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:34982025-09-29 10:39:03.726CONICET 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) |
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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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1844614414992408576 |
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13.070432 |