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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Formato: | Articulo |
Lenguaje: | Inglés |
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2014
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Acceso en línea: | http://sedici.unlp.edu.ar/handle/10915/123626 |
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I19-R120-10915-123626 |
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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 |
bdutipo_str |
Repositorios |
_version_ |
1764820449882013698 |