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
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/174498

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spelling 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
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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
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