Osteoblastic protein tyrosine phosphatases inhibition and connexin 43 phosphorylation by alendronate

Autores
Lezcano, Virginia Alicia; Bellido, Teresita; Plotkin, L. I.; Boland, Ricardo Leopoldo; Morelli, Susana Ana
Año de publicación
2014
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Bisphosphonates (BPs), potent inhibitors of bone resorption which inhibit osteoclasts, have also been shown to act on osteocytes and osteoblasts preventing apoptosis via connexin (Cx) 43 hemichannels and activating the extracellular signal regulated kinases ERKs. We previously demonstrated the presence of a saturable, specific and high affinity binding site for alendronate (ALN) in osteoblastic cells which express Cx43. However, cells lacking Cx43 also bound BPs. Herein we show that bound [3H]-alendronate is displaced by phosphatase substrates. Moreover, similar to Na3VO4, ALN inhibited the activity of transmembrane and cytoplasmic PTPs, pointing out the catalytic domain of phosphatases as a putative BP target. In addition, anti-phospho-tyrosine immunoblot analysis revealed that ALN stimulates tyrosine phosphorylation of several proteins of whole cell lysates, among which the major targets of the BP could be immunochemically identified as Cx43. Additionally, the transmembrane receptor-like PTPs, RPTPµ and RPTPα, as well as the cytoplasmic PTP1B, are highly expressed in ROS 17/2.8 cells. Furthermore, we evidenced that Cx43 interacts with RPTPµ in ROS 17/2.8 and ALN decreases their association. These results support the hypothesis that BPs bind and inhibit PTPs associated to Cx43 or not, which would lead to the activation of signaling pathways in osteoblasts.
Fil: Lezcano, Virginia Alicia. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Bellido, Teresita. Indiana University; Estados Unidos
Fil: Plotkin, L. I.. Indiana University; Estados Unidos
Fil: Boland, Ricardo Leopoldo. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Morelli, Susana Ana. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Materia
Alendronate
Osteoblasts
Cx43 Hemichannels
Protein Tyrosine Phosphatases
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:11336/21688
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/21688
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Osteoblastic protein tyrosine phosphatases inhibition and connexin 43 phosphorylation by alendronateLezcano, Virginia AliciaBellido, TeresitaPlotkin, L. I.Boland, Ricardo LeopoldoMorelli, Susana AnaAlendronateOsteoblastsCx43 HemichannelsProtein Tyrosine Phosphataseshttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Bisphosphonates (BPs), potent inhibitors of bone resorption which inhibit osteoclasts, have also been shown to act on osteocytes and osteoblasts preventing apoptosis via connexin (Cx) 43 hemichannels and activating the extracellular signal regulated kinases ERKs. We previously demonstrated the presence of a saturable, specific and high affinity binding site for alendronate (ALN) in osteoblastic cells which express Cx43. However, cells lacking Cx43 also bound BPs. Herein we show that bound [3H]-alendronate is displaced by phosphatase substrates. Moreover, similar to Na3VO4, ALN inhibited the activity of transmembrane and cytoplasmic PTPs, pointing out the catalytic domain of phosphatases as a putative BP target. In addition, anti-phospho-tyrosine immunoblot analysis revealed that ALN stimulates tyrosine phosphorylation of several proteins of whole cell lysates, among which the major targets of the BP could be immunochemically identified as Cx43. Additionally, the transmembrane receptor-like PTPs, RPTPµ and RPTPα, as well as the cytoplasmic PTP1B, are highly expressed in ROS 17/2.8 cells. Furthermore, we evidenced that Cx43 interacts with RPTPµ in ROS 17/2.8 and ALN decreases their association. These results support the hypothesis that BPs bind and inhibit PTPs associated to Cx43 or not, which would lead to the activation of signaling pathways in osteoblasts.Fil: Lezcano, Virginia Alicia. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Bellido, Teresita. Indiana University; Estados UnidosFil: Plotkin, L. I.. Indiana University; Estados UnidosFil: Boland, Ricardo Leopoldo. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Morelli, Susana Ana. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaElsevier2014-05info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/21688Lezcano, Virginia Alicia; Bellido, Teresita; Plotkin, L. I.; Boland, Ricardo Leopoldo; Morelli, Susana Ana; Osteoblastic protein tyrosine phosphatases inhibition and connexin 43 phosphorylation by alendronate; Elsevier; Experimental Cell Research; 324; 1; 5-2014; 30-390014-4827CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/http://www.sciencedirect.com/science/article/pii/S0014482714001323info:eu-repo/semantics/altIdentifier/doi/10.1016/j.yexcr.2014.03.016info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T10:09:12Zoai:ri.conicet.gov.ar:11336/21688instacron: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:34982025-09-03 10:09:12.642CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Osteoblastic protein tyrosine phosphatases inhibition and connexin 43 phosphorylation by alendronate
title Osteoblastic protein tyrosine phosphatases inhibition and connexin 43 phosphorylation by alendronate
spellingShingle Osteoblastic protein tyrosine phosphatases inhibition and connexin 43 phosphorylation by alendronate
Lezcano, Virginia Alicia
Alendronate
Osteoblasts
Cx43 Hemichannels
Protein Tyrosine Phosphatases
title_short Osteoblastic protein tyrosine phosphatases inhibition and connexin 43 phosphorylation by alendronate
title_full Osteoblastic protein tyrosine phosphatases inhibition and connexin 43 phosphorylation by alendronate
title_fullStr Osteoblastic protein tyrosine phosphatases inhibition and connexin 43 phosphorylation by alendronate
title_full_unstemmed Osteoblastic protein tyrosine phosphatases inhibition and connexin 43 phosphorylation by alendronate
title_sort Osteoblastic protein tyrosine phosphatases inhibition and connexin 43 phosphorylation by alendronate
dc.creator.none.fl_str_mv Lezcano, Virginia Alicia
Bellido, Teresita
Plotkin, L. I.
Boland, Ricardo Leopoldo
Morelli, Susana Ana
author Lezcano, Virginia Alicia
author_facet Lezcano, Virginia Alicia
Bellido, Teresita
Plotkin, L. I.
Boland, Ricardo Leopoldo
Morelli, Susana Ana
author_role author
author2 Bellido, Teresita
Plotkin, L. I.
Boland, Ricardo Leopoldo
Morelli, Susana Ana
author2_role author
author
author
author
dc.subject.none.fl_str_mv Alendronate
Osteoblasts
Cx43 Hemichannels
Protein Tyrosine Phosphatases
topic Alendronate
Osteoblasts
Cx43 Hemichannels
Protein Tyrosine Phosphatases
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Bisphosphonates (BPs), potent inhibitors of bone resorption which inhibit osteoclasts, have also been shown to act on osteocytes and osteoblasts preventing apoptosis via connexin (Cx) 43 hemichannels and activating the extracellular signal regulated kinases ERKs. We previously demonstrated the presence of a saturable, specific and high affinity binding site for alendronate (ALN) in osteoblastic cells which express Cx43. However, cells lacking Cx43 also bound BPs. Herein we show that bound [3H]-alendronate is displaced by phosphatase substrates. Moreover, similar to Na3VO4, ALN inhibited the activity of transmembrane and cytoplasmic PTPs, pointing out the catalytic domain of phosphatases as a putative BP target. In addition, anti-phospho-tyrosine immunoblot analysis revealed that ALN stimulates tyrosine phosphorylation of several proteins of whole cell lysates, among which the major targets of the BP could be immunochemically identified as Cx43. Additionally, the transmembrane receptor-like PTPs, RPTPµ and RPTPα, as well as the cytoplasmic PTP1B, are highly expressed in ROS 17/2.8 cells. Furthermore, we evidenced that Cx43 interacts with RPTPµ in ROS 17/2.8 and ALN decreases their association. These results support the hypothesis that BPs bind and inhibit PTPs associated to Cx43 or not, which would lead to the activation of signaling pathways in osteoblasts.
Fil: Lezcano, Virginia Alicia. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Bellido, Teresita. Indiana University; Estados Unidos
Fil: Plotkin, L. I.. Indiana University; Estados Unidos
Fil: Boland, Ricardo Leopoldo. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Morelli, Susana Ana. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
description Bisphosphonates (BPs), potent inhibitors of bone resorption which inhibit osteoclasts, have also been shown to act on osteocytes and osteoblasts preventing apoptosis via connexin (Cx) 43 hemichannels and activating the extracellular signal regulated kinases ERKs. We previously demonstrated the presence of a saturable, specific and high affinity binding site for alendronate (ALN) in osteoblastic cells which express Cx43. However, cells lacking Cx43 also bound BPs. Herein we show that bound [3H]-alendronate is displaced by phosphatase substrates. Moreover, similar to Na3VO4, ALN inhibited the activity of transmembrane and cytoplasmic PTPs, pointing out the catalytic domain of phosphatases as a putative BP target. In addition, anti-phospho-tyrosine immunoblot analysis revealed that ALN stimulates tyrosine phosphorylation of several proteins of whole cell lysates, among which the major targets of the BP could be immunochemically identified as Cx43. Additionally, the transmembrane receptor-like PTPs, RPTPµ and RPTPα, as well as the cytoplasmic PTP1B, are highly expressed in ROS 17/2.8 cells. Furthermore, we evidenced that Cx43 interacts with RPTPµ in ROS 17/2.8 and ALN decreases their association. These results support the hypothesis that BPs bind and inhibit PTPs associated to Cx43 or not, which would lead to the activation of signaling pathways in osteoblasts.
publishDate 2014
dc.date.none.fl_str_mv 2014-05
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/11336/21688
Lezcano, Virginia Alicia; Bellido, Teresita; Plotkin, L. I.; Boland, Ricardo Leopoldo; Morelli, Susana Ana; Osteoblastic protein tyrosine phosphatases inhibition and connexin 43 phosphorylation by alendronate; Elsevier; Experimental Cell Research; 324; 1; 5-2014; 30-39
0014-4827
CONICET Digital
CONICET
url http://hdl.handle.net/11336/21688
identifier_str_mv Lezcano, Virginia Alicia; Bellido, Teresita; Plotkin, L. I.; Boland, Ricardo Leopoldo; Morelli, Susana Ana; Osteoblastic protein tyrosine phosphatases inhibition and connexin 43 phosphorylation by alendronate; Elsevier; Experimental Cell Research; 324; 1; 5-2014; 30-39
0014-4827
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/http://www.sciencedirect.com/science/article/pii/S0014482714001323
info:eu-repo/semantics/altIdentifier/doi/10.1016/j.yexcr.2014.03.016
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
application/pdf
dc.publisher.none.fl_str_mv Elsevier
publisher.none.fl_str_mv Elsevier
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 13.13397

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