Progesterone (Pg) and Medroxyprogesterone acetate (MPA) regulate same events with opposite actions in bone and vascular cells
- Autores
- Cutini, Pablo Hernan; Campelo, Adrián Esteban; Massheimer, Virginia Laura
- Año de publicación
- 2020
- Idioma
- inglés
- Tipo de recurso
- documento de conferencia
- Estado
- versión publicada
- Descripción
- Bone and cardiovascular diseases are multifactorial clinical entities that often coexist in postmenopausal women. Clinical and epidemiological studies have shown an interesting relationship between high bone turnover and cardiovascular disease mortality. Disorders in bone metabolism reversely correlate with vascular calcification (VCa). Hormone replacement therapy including natural Pg or synthetic progestins such as MPA emerged as a therapeutic option, although the risk/benefit of its use is controversial. VCa developed within atherosclerotic plaque is partly due to the osteogenic transdifferentiation of vascular smooth muscle cells (VSMC). The aim of this work was to investigate the effect of Pg and MPA on cellular/molecular events involved in VCa and in osteoblastogenesis. Primary cultures of calvarial osteoblasts (OB) and aortic VSMC, were in vitro exposed to 10 nM Pg or 10 nM MPA. Measurements of matrix extracellular calcium content and alkaline phosphatase (ALP) activity were employed as osteoblastic differentiation markers. In order to promote osteoblastic differentiation, VSMC were cultured for 21 days in osteogenic medium (10 mM β-glycerophosphate and 4 mM CaCl2). When VSMC were cultured in osteogenic medium (VSMC-OB), treatment with Pg for 21 days significantly reduced ALP activity (15% below control, p<0.02) and calcium content (32% below control, p<0.02). Similar treatment with the synthetic progestin also showed a significant reduction in ALP activity (239.9 ± 21.0 vs. 159.6 ± 19.1 x103 IU/mg protein, control vs MPA, p<0.02), as well as in the extracellular calcium deposition (365.1 ± 38.2 vs 253.6 ± 21.9 µg/mg protein, control vs MPA, p<0.02). Conversely, exposure of OB cells to Pg or MPA significantly increased ALP activity (59%; 290% above control, Pg; MPA, p<0.02) and matrix calcium levels (12%; 55% above control, Pg; MPA, p<0.02). The mechanism of action of Pg and MPA on both cells involves the participation of Pg receptor (PgR), since pre-treatment of cells with RU486, a PgR antagonist, completely reversed the hormonal action. However, we ruled out the involvement of the androgen receptor (AR), since in the presence of the AR antagonist flutamide, the effect of the progestogens was sustained. In conclusion, although Pg and MPA exert opposite effects on OB and VSMC-OB, both steroids would exhibit a potential beneficial effect by promoting osteoblastic differentiation and inhibiting VCa.
Fil: Cutini, Pablo Hernan. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Ciencias Biológicas y Biomédicas del Sur. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia. Instituto de Ciencias Biológicas y Biomédicas del Sur; Argentina
Fil: Campelo, Adrián Esteban. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Ciencias Biológicas y Biomédicas del Sur. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia. Instituto de Ciencias Biológicas y Biomédicas del Sur; Argentina
Fil: Massheimer, Virginia Laura. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Ciencias Biológicas y Biomédicas del Sur. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia. Instituto de Ciencias Biológicas y Biomédicas del Sur; Argentina
2020 Annual Meeting of the American Society for Bone and Mineral Research
Estados Unidos
American Society for Bone and Mineral Research - Materia
-
VASCULAR CALCIFICATION
VASCULAR SMOOTH MUSCLE CELLS
OSTEOBLASTS
PROGESTINS - 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:11336/174498
Ver los metadatos del registro completo
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Progesterone (Pg) and Medroxyprogesterone acetate (MPA) regulate same events with opposite actions in bone and vascular cellsCutini, Pablo HernanCampelo, Adrián EstebanMassheimer, Virginia LauraVASCULAR CALCIFICATIONVASCULAR SMOOTH MUSCLE CELLSOSTEOBLASTSPROGESTINShttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Bone and cardiovascular diseases are multifactorial clinical entities that often coexist in postmenopausal women. Clinical and epidemiological studies have shown an interesting relationship between high bone turnover and cardiovascular disease mortality. Disorders in bone metabolism reversely correlate with vascular calcification (VCa). Hormone replacement therapy including natural Pg or synthetic progestins such as MPA emerged as a therapeutic option, although the risk/benefit of its use is controversial. VCa developed within atherosclerotic plaque is partly due to the osteogenic transdifferentiation of vascular smooth muscle cells (VSMC). The aim of this work was to investigate the effect of Pg and MPA on cellular/molecular events involved in VCa and in osteoblastogenesis. Primary cultures of calvarial osteoblasts (OB) and aortic VSMC, were in vitro exposed to 10 nM Pg or 10 nM MPA. Measurements of matrix extracellular calcium content and alkaline phosphatase (ALP) activity were employed as osteoblastic differentiation markers. In order to promote osteoblastic differentiation, VSMC were cultured for 21 days in osteogenic medium (10 mM β-glycerophosphate and 4 mM CaCl2). When VSMC were cultured in osteogenic medium (VSMC-OB), treatment with Pg for 21 days significantly reduced ALP activity (15% below control, p<0.02) and calcium content (32% below control, p<0.02). Similar treatment with the synthetic progestin also showed a significant reduction in ALP activity (239.9 ± 21.0 vs. 159.6 ± 19.1 x103 IU/mg protein, control vs MPA, p<0.02), as well as in the extracellular calcium deposition (365.1 ± 38.2 vs 253.6 ± 21.9 µg/mg protein, control vs MPA, p<0.02). Conversely, exposure of OB cells to Pg or MPA significantly increased ALP activity (59%; 290% above control, Pg; MPA, p<0.02) and matrix calcium levels (12%; 55% above control, Pg; MPA, p<0.02). The mechanism of action of Pg and MPA on both cells involves the participation of Pg receptor (PgR), since pre-treatment of cells with RU486, a PgR antagonist, completely reversed the hormonal action. However, we ruled out the involvement of the androgen receptor (AR), since in the presence of the AR antagonist flutamide, the effect of the progestogens was sustained. In conclusion, although Pg and MPA exert opposite effects on OB and VSMC-OB, both steroids would exhibit a potential beneficial effect by promoting osteoblastic differentiation and inhibiting VCa.Fil: Cutini, Pablo Hernan. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Ciencias Biológicas y Biomédicas del Sur. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia. Instituto de Ciencias Biológicas y Biomédicas del Sur; ArgentinaFil: Campelo, Adrián Esteban. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Ciencias Biológicas y Biomédicas del Sur. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia. Instituto de Ciencias Biológicas y Biomédicas del Sur; ArgentinaFil: Massheimer, Virginia Laura. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Ciencias Biológicas y Biomédicas del Sur. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia. Instituto de Ciencias Biológicas y Biomédicas del Sur; Argentina2020 Annual Meeting of the American Society for Bone and Mineral ResearchEstados UnidosAmerican Society for Bone and Mineral ResearchWileyCivitelli, Roberto2020info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/conferenceObjectReuniónJournalhttp://purl.org/coar/resource_type/c_5794info:ar-repo/semantics/documentoDeConferenciatext/plainapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/174498Progesterone (Pg) and Medroxyprogesterone acetate (MPA) regulate same events with opposite actions in bone and vascular cells; 2020 Annual Meeting of the American Society for Bone and Mineral Research; Estados Unidos; 2020; 1-50884-0431CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1002/jbmr.4206info:eu-repo/semantics/altIdentifier/url/https://asbmr.onlinelibrary.wiley.com/doi/10.1002/jbmr.4206Internacionalinfo:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T10:11:30Zoai:ri.conicet.gov.ar:11336/174498instacron: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 10:11:30.371CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse |
dc.title.none.fl_str_mv |
Progesterone (Pg) and Medroxyprogesterone acetate (MPA) regulate same events with opposite actions in bone and vascular cells |
title |
Progesterone (Pg) and Medroxyprogesterone acetate (MPA) regulate same events with opposite actions in bone and vascular cells |
spellingShingle |
Progesterone (Pg) and Medroxyprogesterone acetate (MPA) regulate same events with opposite actions in bone and vascular cells Cutini, Pablo Hernan VASCULAR CALCIFICATION VASCULAR SMOOTH MUSCLE CELLS OSTEOBLASTS PROGESTINS |
title_short |
Progesterone (Pg) and Medroxyprogesterone acetate (MPA) regulate same events with opposite actions in bone and vascular cells |
title_full |
Progesterone (Pg) and Medroxyprogesterone acetate (MPA) regulate same events with opposite actions in bone and vascular cells |
title_fullStr |
Progesterone (Pg) and Medroxyprogesterone acetate (MPA) regulate same events with opposite actions in bone and vascular cells |
title_full_unstemmed |
Progesterone (Pg) and Medroxyprogesterone acetate (MPA) regulate same events with opposite actions in bone and vascular cells |
title_sort |
Progesterone (Pg) and Medroxyprogesterone acetate (MPA) regulate same events with opposite actions in bone and vascular cells |
dc.creator.none.fl_str_mv |
Cutini, Pablo Hernan Campelo, Adrián Esteban Massheimer, Virginia Laura |
author |
Cutini, Pablo Hernan |
author_facet |
Cutini, Pablo Hernan Campelo, Adrián Esteban Massheimer, Virginia Laura |
author_role |
author |
author2 |
Campelo, Adrián Esteban Massheimer, Virginia Laura |
author2_role |
author author |
dc.contributor.none.fl_str_mv |
Civitelli, Roberto |
dc.subject.none.fl_str_mv |
VASCULAR CALCIFICATION VASCULAR SMOOTH MUSCLE CELLS OSTEOBLASTS PROGESTINS |
topic |
VASCULAR CALCIFICATION VASCULAR SMOOTH MUSCLE CELLS OSTEOBLASTS PROGESTINS |
purl_subject.fl_str_mv |
https://purl.org/becyt/ford/1.6 https://purl.org/becyt/ford/1 |
dc.description.none.fl_txt_mv |
Bone and cardiovascular diseases are multifactorial clinical entities that often coexist in postmenopausal women. Clinical and epidemiological studies have shown an interesting relationship between high bone turnover and cardiovascular disease mortality. Disorders in bone metabolism reversely correlate with vascular calcification (VCa). Hormone replacement therapy including natural Pg or synthetic progestins such as MPA emerged as a therapeutic option, although the risk/benefit of its use is controversial. VCa developed within atherosclerotic plaque is partly due to the osteogenic transdifferentiation of vascular smooth muscle cells (VSMC). The aim of this work was to investigate the effect of Pg and MPA on cellular/molecular events involved in VCa and in osteoblastogenesis. Primary cultures of calvarial osteoblasts (OB) and aortic VSMC, were in vitro exposed to 10 nM Pg or 10 nM MPA. Measurements of matrix extracellular calcium content and alkaline phosphatase (ALP) activity were employed as osteoblastic differentiation markers. In order to promote osteoblastic differentiation, VSMC were cultured for 21 days in osteogenic medium (10 mM β-glycerophosphate and 4 mM CaCl2). When VSMC were cultured in osteogenic medium (VSMC-OB), treatment with Pg for 21 days significantly reduced ALP activity (15% below control, p<0.02) and calcium content (32% below control, p<0.02). Similar treatment with the synthetic progestin also showed a significant reduction in ALP activity (239.9 ± 21.0 vs. 159.6 ± 19.1 x103 IU/mg protein, control vs MPA, p<0.02), as well as in the extracellular calcium deposition (365.1 ± 38.2 vs 253.6 ± 21.9 µg/mg protein, control vs MPA, p<0.02). Conversely, exposure of OB cells to Pg or MPA significantly increased ALP activity (59%; 290% above control, Pg; MPA, p<0.02) and matrix calcium levels (12%; 55% above control, Pg; MPA, p<0.02). The mechanism of action of Pg and MPA on both cells involves the participation of Pg receptor (PgR), since pre-treatment of cells with RU486, a PgR antagonist, completely reversed the hormonal action. However, we ruled out the involvement of the androgen receptor (AR), since in the presence of the AR antagonist flutamide, the effect of the progestogens was sustained. In conclusion, although Pg and MPA exert opposite effects on OB and VSMC-OB, both steroids would exhibit a potential beneficial effect by promoting osteoblastic differentiation and inhibiting VCa. Fil: Cutini, Pablo Hernan. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Ciencias Biológicas y Biomédicas del Sur. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia. Instituto de Ciencias Biológicas y Biomédicas del Sur; Argentina Fil: Campelo, Adrián Esteban. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Ciencias Biológicas y Biomédicas del Sur. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia. Instituto de Ciencias Biológicas y Biomédicas del Sur; Argentina Fil: Massheimer, Virginia Laura. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Ciencias Biológicas y Biomédicas del Sur. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia. Instituto de Ciencias Biológicas y Biomédicas del Sur; Argentina 2020 Annual Meeting of the American Society for Bone and Mineral Research Estados Unidos American Society for Bone and Mineral Research |
description |
Bone and cardiovascular diseases are multifactorial clinical entities that often coexist in postmenopausal women. Clinical and epidemiological studies have shown an interesting relationship between high bone turnover and cardiovascular disease mortality. Disorders in bone metabolism reversely correlate with vascular calcification (VCa). Hormone replacement therapy including natural Pg or synthetic progestins such as MPA emerged as a therapeutic option, although the risk/benefit of its use is controversial. VCa developed within atherosclerotic plaque is partly due to the osteogenic transdifferentiation of vascular smooth muscle cells (VSMC). The aim of this work was to investigate the effect of Pg and MPA on cellular/molecular events involved in VCa and in osteoblastogenesis. Primary cultures of calvarial osteoblasts (OB) and aortic VSMC, were in vitro exposed to 10 nM Pg or 10 nM MPA. Measurements of matrix extracellular calcium content and alkaline phosphatase (ALP) activity were employed as osteoblastic differentiation markers. In order to promote osteoblastic differentiation, VSMC were cultured for 21 days in osteogenic medium (10 mM β-glycerophosphate and 4 mM CaCl2). When VSMC were cultured in osteogenic medium (VSMC-OB), treatment with Pg for 21 days significantly reduced ALP activity (15% below control, p<0.02) and calcium content (32% below control, p<0.02). Similar treatment with the synthetic progestin also showed a significant reduction in ALP activity (239.9 ± 21.0 vs. 159.6 ± 19.1 x103 IU/mg protein, control vs MPA, p<0.02), as well as in the extracellular calcium deposition (365.1 ± 38.2 vs 253.6 ± 21.9 µg/mg protein, control vs MPA, p<0.02). Conversely, exposure of OB cells to Pg or MPA significantly increased ALP activity (59%; 290% above control, Pg; MPA, p<0.02) and matrix calcium levels (12%; 55% above control, Pg; MPA, p<0.02). The mechanism of action of Pg and MPA on both cells involves the participation of Pg receptor (PgR), since pre-treatment of cells with RU486, a PgR antagonist, completely reversed the hormonal action. However, we ruled out the involvement of the androgen receptor (AR), since in the presence of the AR antagonist flutamide, the effect of the progestogens was sustained. In conclusion, although Pg and MPA exert opposite effects on OB and VSMC-OB, both steroids would exhibit a potential beneficial effect by promoting osteoblastic differentiation and inhibiting VCa. |
publishDate |
2020 |
dc.date.none.fl_str_mv |
2020 |
dc.type.none.fl_str_mv |
info:eu-repo/semantics/publishedVersion info:eu-repo/semantics/conferenceObject Reunión Journal http://purl.org/coar/resource_type/c_5794 info:ar-repo/semantics/documentoDeConferencia |
status_str |
publishedVersion |
format |
conferenceObject |
dc.identifier.none.fl_str_mv |
http://hdl.handle.net/11336/174498 Progesterone (Pg) and Medroxyprogesterone acetate (MPA) regulate same events with opposite actions in bone and vascular cells; 2020 Annual Meeting of the American Society for Bone and Mineral Research; Estados Unidos; 2020; 1-5 0884-0431 CONICET Digital CONICET |
url |
http://hdl.handle.net/11336/174498 |
identifier_str_mv |
Progesterone (Pg) and Medroxyprogesterone acetate (MPA) regulate same events with opposite actions in bone and vascular cells; 2020 Annual Meeting of the American Society for Bone and Mineral Research; Estados Unidos; 2020; 1-5 0884-0431 CONICET Digital CONICET |
dc.language.none.fl_str_mv |
eng |
language |
eng |
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info:eu-repo/semantics/altIdentifier/doi/10.1002/jbmr.4206 info:eu-repo/semantics/altIdentifier/url/https://asbmr.onlinelibrary.wiley.com/doi/10.1002/jbmr.4206 |
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Internacional |
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Wiley |
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Wiley |
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reponame:CONICET Digital (CONICET) instname:Consejo Nacional de Investigaciones Científicas y Técnicas |
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