Strontium ranelate stimulates the activity of bone-specific alkaline phosphatase: interaction with Zn2+ and Mg2+

Autores
Fernández, Juan Manuel; Molinuevo, María Silvina; McCarthy, Antonio Desmond; Cortizo, Ana María
Año de publicación
2014
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Strontium ranelate (SR) is an orally administered and bone-targeting anti-osteoporotic agent that increases osteoblast-mediated bone formation while decreasing osteoclastic bone resorption, and thus reduces the risk of vertebral and femoral bone fractures in postmenopausal women with osteoporosis. Osteoblastic alkaline phosphatase (ALP) is a key enzyme involved in the process of bone formation and osteoid mineralization. In this study we investigated the direct effect of strontium (SR and SrCl2) on the activity of ALP obtained from UMR106 osteosarcoma cells, as well as its possible interactions with the divalent cations Zn2+ and Mg2+. In the presence of Mg2+, both SR and SrCl2 (0.05–0.5 mM) significantly increased ALP activity (15–66 % above basal), and this was dose-dependent in the case of SR. The stimulatory effect of strontium disappeared in the absence of Mg2+. The cofactor Zn2+ also increased ALP activity (an effect that reached a plateau at 2 mM), and co-incubation of 2 mM Zn2+ with 0.05–0.5 mM SR showed an additive effect on ALP activity stimulation. SR induced a dose-dependent decrease in the Km of ALP (and thus an increase in affinity for its substrate) with a maximal effect at 0.1 mM. Co-incubation with 2 mM Zn2+ further decreased Km in all cases. These direct effects of SR on osteoblastic ALP activity could be indicating an alternative mechanism by which this compound may regulate bone matrix mineralization.
Fil: Fernández, Juan Manuel. Universidad Nacional de La Plata. Facultad de Ciencias Exactas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Molinuevo, María Silvina. Universidad Nacional de La Plata. Facultad de Ciencias Exactas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: McCarthy, Antonio Desmond. Universidad Nacional de La Plata. Facultad de Ciencias Exactas; Argentina
Fil: Cortizo, Ana María. Universidad Nacional de La Plata. Facultad de Ciencias Exactas; Argentina
Materia
Strontium Ranelate
Alkaline Phosphatase
Metal Ions
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:11336/31315
Acceder
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network_name_str CONICET Digital (CONICET)
spelling Strontium ranelate stimulates the activity of bone-specific alkaline phosphatase: interaction with Zn2+ and Mg2+Fernández, Juan ManuelMolinuevo, María SilvinaMcCarthy, Antonio DesmondCortizo, Ana MaríaStrontium RanelateAlkaline PhosphataseMetal Ionshttps://purl.org/becyt/ford/3.3https://purl.org/becyt/ford/3Strontium ranelate (SR) is an orally administered and bone-targeting anti-osteoporotic agent that increases osteoblast-mediated bone formation while decreasing osteoclastic bone resorption, and thus reduces the risk of vertebral and femoral bone fractures in postmenopausal women with osteoporosis. Osteoblastic alkaline phosphatase (ALP) is a key enzyme involved in the process of bone formation and osteoid mineralization. In this study we investigated the direct effect of strontium (SR and SrCl2) on the activity of ALP obtained from UMR106 osteosarcoma cells, as well as its possible interactions with the divalent cations Zn2+ and Mg2+. In the presence of Mg2+, both SR and SrCl2 (0.05–0.5 mM) significantly increased ALP activity (15–66 % above basal), and this was dose-dependent in the case of SR. The stimulatory effect of strontium disappeared in the absence of Mg2+. The cofactor Zn2+ also increased ALP activity (an effect that reached a plateau at 2 mM), and co-incubation of 2 mM Zn2+ with 0.05–0.5 mM SR showed an additive effect on ALP activity stimulation. SR induced a dose-dependent decrease in the Km of ALP (and thus an increase in affinity for its substrate) with a maximal effect at 0.1 mM. Co-incubation with 2 mM Zn2+ further decreased Km in all cases. These direct effects of SR on osteoblastic ALP activity could be indicating an alternative mechanism by which this compound may regulate bone matrix mineralization.Fil: Fernández, Juan Manuel. Universidad Nacional de La Plata. Facultad de Ciencias Exactas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Molinuevo, María Silvina. Universidad Nacional de La Plata. Facultad de Ciencias Exactas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: McCarthy, Antonio Desmond. Universidad Nacional de La Plata. Facultad de Ciencias Exactas; ArgentinaFil: Cortizo, Ana María. Universidad Nacional de La Plata. Facultad de Ciencias Exactas; ArgentinaSpringer2014-04info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/31315Cortizo, Ana María; McCarthy, Antonio Desmond; Molinuevo, María Silvina; Fernández, Juan Manuel; Strontium ranelate stimulates the activity of bone-specific alkaline phosphatase: interaction with Zn2+ and Mg2+; Springer; Biometals; 27; 3; 4-2014; 601-6070966-08441572-8773CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/http://link.springer.com/article/10.1007%2Fs10534-014-9733-8info:eu-repo/semantics/altIdentifier/doi/10.1007/s10534-014-9733-8info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T09:56:05Zoai:ri.conicet.gov.ar:11336/31315instacron: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 09:56:06.025CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Strontium ranelate stimulates the activity of bone-specific alkaline phosphatase: interaction with Zn2+ and Mg2+
title Strontium ranelate stimulates the activity of bone-specific alkaline phosphatase: interaction with Zn2+ and Mg2+
spellingShingle Strontium ranelate stimulates the activity of bone-specific alkaline phosphatase: interaction with Zn2+ and Mg2+
Fernández, Juan Manuel
Strontium Ranelate
Alkaline Phosphatase
Metal Ions
title_short Strontium ranelate stimulates the activity of bone-specific alkaline phosphatase: interaction with Zn2+ and Mg2+
title_full Strontium ranelate stimulates the activity of bone-specific alkaline phosphatase: interaction with Zn2+ and Mg2+
title_fullStr Strontium ranelate stimulates the activity of bone-specific alkaline phosphatase: interaction with Zn2+ and Mg2+
title_full_unstemmed Strontium ranelate stimulates the activity of bone-specific alkaline phosphatase: interaction with Zn2+ and Mg2+
title_sort Strontium ranelate stimulates the activity of bone-specific alkaline phosphatase: interaction with Zn2+ and Mg2+
dc.creator.none.fl_str_mv Fernández, Juan Manuel
Molinuevo, María Silvina
McCarthy, Antonio Desmond
Cortizo, Ana María
author Fernández, Juan Manuel
author_facet Fernández, Juan Manuel
Molinuevo, María Silvina
McCarthy, Antonio Desmond
Cortizo, Ana María
author_role author
author2 Molinuevo, María Silvina
McCarthy, Antonio Desmond
Cortizo, Ana María
author2_role author
author
author
dc.subject.none.fl_str_mv Strontium Ranelate
Alkaline Phosphatase
Metal Ions
topic Strontium Ranelate
Alkaline Phosphatase
Metal Ions
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.3
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Strontium ranelate (SR) is an orally administered and bone-targeting anti-osteoporotic agent that increases osteoblast-mediated bone formation while decreasing osteoclastic bone resorption, and thus reduces the risk of vertebral and femoral bone fractures in postmenopausal women with osteoporosis. Osteoblastic alkaline phosphatase (ALP) is a key enzyme involved in the process of bone formation and osteoid mineralization. In this study we investigated the direct effect of strontium (SR and SrCl2) on the activity of ALP obtained from UMR106 osteosarcoma cells, as well as its possible interactions with the divalent cations Zn2+ and Mg2+. In the presence of Mg2+, both SR and SrCl2 (0.05–0.5 mM) significantly increased ALP activity (15–66 % above basal), and this was dose-dependent in the case of SR. The stimulatory effect of strontium disappeared in the absence of Mg2+. The cofactor Zn2+ also increased ALP activity (an effect that reached a plateau at 2 mM), and co-incubation of 2 mM Zn2+ with 0.05–0.5 mM SR showed an additive effect on ALP activity stimulation. SR induced a dose-dependent decrease in the Km of ALP (and thus an increase in affinity for its substrate) with a maximal effect at 0.1 mM. Co-incubation with 2 mM Zn2+ further decreased Km in all cases. These direct effects of SR on osteoblastic ALP activity could be indicating an alternative mechanism by which this compound may regulate bone matrix mineralization.
Fil: Fernández, Juan Manuel. Universidad Nacional de La Plata. Facultad de Ciencias Exactas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Molinuevo, María Silvina. Universidad Nacional de La Plata. Facultad de Ciencias Exactas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: McCarthy, Antonio Desmond. Universidad Nacional de La Plata. Facultad de Ciencias Exactas; Argentina
Fil: Cortizo, Ana María. Universidad Nacional de La Plata. Facultad de Ciencias Exactas; Argentina
description Strontium ranelate (SR) is an orally administered and bone-targeting anti-osteoporotic agent that increases osteoblast-mediated bone formation while decreasing osteoclastic bone resorption, and thus reduces the risk of vertebral and femoral bone fractures in postmenopausal women with osteoporosis. Osteoblastic alkaline phosphatase (ALP) is a key enzyme involved in the process of bone formation and osteoid mineralization. In this study we investigated the direct effect of strontium (SR and SrCl2) on the activity of ALP obtained from UMR106 osteosarcoma cells, as well as its possible interactions with the divalent cations Zn2+ and Mg2+. In the presence of Mg2+, both SR and SrCl2 (0.05–0.5 mM) significantly increased ALP activity (15–66 % above basal), and this was dose-dependent in the case of SR. The stimulatory effect of strontium disappeared in the absence of Mg2+. The cofactor Zn2+ also increased ALP activity (an effect that reached a plateau at 2 mM), and co-incubation of 2 mM Zn2+ with 0.05–0.5 mM SR showed an additive effect on ALP activity stimulation. SR induced a dose-dependent decrease in the Km of ALP (and thus an increase in affinity for its substrate) with a maximal effect at 0.1 mM. Co-incubation with 2 mM Zn2+ further decreased Km in all cases. These direct effects of SR on osteoblastic ALP activity could be indicating an alternative mechanism by which this compound may regulate bone matrix mineralization.
publishDate 2014
dc.date.none.fl_str_mv 2014-04
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/11336/31315
Cortizo, Ana María; McCarthy, Antonio Desmond; Molinuevo, María Silvina; Fernández, Juan Manuel; Strontium ranelate stimulates the activity of bone-specific alkaline phosphatase: interaction with Zn2+ and Mg2+; Springer; Biometals; 27; 3; 4-2014; 601-607
0966-0844
1572-8773
CONICET Digital
CONICET
url http://hdl.handle.net/11336/31315
identifier_str_mv Cortizo, Ana María; McCarthy, Antonio Desmond; Molinuevo, María Silvina; Fernández, Juan Manuel; Strontium ranelate stimulates the activity of bone-specific alkaline phosphatase: interaction with Zn2+ and Mg2+; Springer; Biometals; 27; 3; 4-2014; 601-607
0966-0844
1572-8773
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://link.springer.com/article/10.1007%2Fs10534-014-9733-8
info:eu-repo/semantics/altIdentifier/doi/10.1007/s10534-014-9733-8
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
dc.publisher.none.fl_str_mv Springer
publisher.none.fl_str_mv Springer
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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