Strontium ranelate stimulates the activity of bone-specific alkaline phosphatase: interaction with Zn ²⁺ and Mg ²⁺

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. O...

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Detalles Bibliográficos
Autores principales: Fernández, Juan Manuel, Molinuevo, María Silvina, McCarthy, Antonio Desmond, Cortizo, Ana María
Formato: Articulo
Lenguaje:Inglés
Publicado: 2014
Materias:
Acceso en línea:http://sedici.unlp.edu.ar/handle/10915/123626
Aporte de:
id I19-R120-10915-123626
record_format dspace
institution Universidad Nacional de La Plata
institution_str I-19
repository_str R-120
collection SEDICI (UNLP)
language Inglés
topic Biología
Ciencias Médicas
Bone-specific alkaline phosphatase
Magnesium
Zinc
Strontium ranelate
Osteoblasts
spellingShingle Biología
Ciencias Médicas
Bone-specific alkaline phosphatase
Magnesium
Zinc
Strontium ranelate
Osteoblasts
Fernández, Juan Manuel
Molinuevo, María Silvina
McCarthy, Antonio Desmond
Cortizo, Ana María
Strontium ranelate stimulates the activity of bone-specific alkaline phosphatase: interaction with Zn ²⁺ and Mg ²⁺
topic_facet Biología
Ciencias Médicas
Bone-specific alkaline phosphatase
Magnesium
Zinc
Strontium ranelate
Osteoblasts
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.
format Articulo
Articulo
author Fernández, Juan Manuel
Molinuevo, María Silvina
McCarthy, Antonio Desmond
Cortizo, Ana María
author_facet Fernández, Juan Manuel
Molinuevo, María Silvina
McCarthy, Antonio Desmond
Cortizo, Ana María
author_sort Fernández, Juan Manuel
title Strontium ranelate stimulates the activity of bone-specific alkaline phosphatase: interaction with Zn ²⁺ and Mg ²⁺
title_short Strontium ranelate stimulates the activity of bone-specific alkaline phosphatase: interaction with Zn ²⁺ and Mg ²⁺
title_full Strontium ranelate stimulates the activity of bone-specific alkaline phosphatase: interaction with Zn ²⁺ and Mg ²⁺
title_fullStr Strontium ranelate stimulates the activity of bone-specific alkaline phosphatase: interaction with Zn ²⁺ and Mg ²⁺
title_full_unstemmed Strontium ranelate stimulates the activity of bone-specific alkaline phosphatase: interaction with Zn ²⁺ and Mg ²⁺
title_sort strontium ranelate stimulates the activity of bone-specific alkaline phosphatase: interaction with zn ²⁺ and mg ²⁺
publishDate 2014
url http://sedici.unlp.edu.ar/handle/10915/123626
work_keys_str_mv AT fernandezjuanmanuel strontiumranelatestimulatestheactivityofbonespecificalkalinephosphataseinteractionwithzn2andmg2
AT molinuevomariasilvina strontiumranelatestimulatestheactivityofbonespecificalkalinephosphataseinteractionwithzn2andmg2
AT mccarthyantoniodesmond strontiumranelatestimulatestheactivityofbonespecificalkalinephosphataseinteractionwithzn2andmg2
AT cortizoanamaria strontiumranelatestimulatestheactivityofbonespecificalkalinephosphataseinteractionwithzn2andmg2
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