Opposing effects of bisphosphonates and advanced glycation end-products on osteoblastic cells

Autores
Gangoiti, María Virginia; Cortizo, Ana María; Arnol, Verónica; Felice, Juan Ignacio; McCarthy, Antonio Desmond
Año de publicación
2008
Idioma
inglés
Tipo de recurso
artículo
Estado
versión enviada
Descripción
Patients with long-standing Diabetes mellitus can develop osteopenia and osteoporosis. We have previously shown that advanced glycation endproducts reduce the bone-forming activity of osteoblasts. Bisphosphonates are used for the treatment of various bone disorders, since they reduce osteoclastic function and survival, and stimulate osteoblastic bone-forming capacity. In this work we have investigated whether bisphosphonates are able to revert advanced glycation endproducts-induced deleterious effects in osteoblasts. MC3T3E1 and UMR106 osteoblastic cells were incubated with control or advanced glycation endproducts-modified bovine serum albumin, in the presence or absence of different doses of the bisphosphonates Alendronate, Pamidronate or Zoledronate. After 24–72 h of culture, we evaluated their effects on cell proliferation and apoptosis, type-1 collagen production, alkaline and neutral phosphatase activity, and intracellular reactive oxygen species production. Advanced glycation endproducts significantly decreased osteoblast proliferation, alkaline phosphatase activity and type 1 collagen production, while increasing osteoblastic apoptosis and reactive oxygen species production. These effects were completely reverted by low doses (10−8 M) of bisphosphonates. High doses of bisphosphonates (10−4–10−5 M) were toxic for osteoblasts. Nifedipine (L-type calcium channel blocker) did not affect the advanced glycation endproducts-induced decrease in osteoblastic proliferation, although it blocked the reversion of this effect by 10−8 M Alendronate. Both advanced glycation endproducts and Alendronate inhibited the activity of intracellular neutral phosphatases. In conclusion, we show that bisphosphonates revert the deleterious actions of advanced glycation endproducts on osteoblastic cells, and that these effects of bisphosphonates depend on: (a) Ca2+ influx through L-type voltage-sensitive channels, and (b) blockage of advanced glycation endproducts-induced reactive oxygen species generation.
Materia
Ciencias Químicas
Bisphosphonates
Advanced glycation endproducts
Osteoblasts
Proliferation
Reactive oxygen species
Nivel de accesibilidad
acceso abierto
Condiciones de uso
http://creativecommons.org/licenses/by/4.0/
Repositorio
CIC Digital (CICBA)
Institución
Comisión de Investigaciones Científicas de la Provincia de Buenos Aires
OAI Identificador
oai:digital.cic.gba.gob.ar:11746/4760

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network_acronym_str CICBA
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network_name_str CIC Digital (CICBA)
spelling Opposing effects of bisphosphonates and advanced glycation end-products on osteoblastic cellsGangoiti, María VirginiaCortizo, Ana MaríaArnol, VerónicaFelice, Juan IgnacioMcCarthy, Antonio DesmondCiencias QuímicasBisphosphonatesAdvanced glycation endproductsOsteoblastsProliferationReactive oxygen speciesPatients with long-standing Diabetes mellitus can develop osteopenia and osteoporosis. We have previously shown that advanced glycation endproducts reduce the bone-forming activity of osteoblasts. Bisphosphonates are used for the treatment of various bone disorders, since they reduce osteoclastic function and survival, and stimulate osteoblastic bone-forming capacity. In this work we have investigated whether bisphosphonates are able to revert advanced glycation endproducts-induced deleterious effects in osteoblasts. MC3T3E1 and UMR106 osteoblastic cells were incubated with control or advanced glycation endproducts-modified bovine serum albumin, in the presence or absence of different doses of the bisphosphonates Alendronate, Pamidronate or Zoledronate. After 24–72 h of culture, we evaluated their effects on cell proliferation and apoptosis, type-1 collagen production, alkaline and neutral phosphatase activity, and intracellular reactive oxygen species production. Advanced glycation endproducts significantly decreased osteoblast proliferation, alkaline phosphatase activity and type 1 collagen production, while increasing osteoblastic apoptosis and reactive oxygen species production. These effects were completely reverted by low doses (10−8 M) of bisphosphonates. High doses of bisphosphonates (10−4–10−5 M) were toxic for osteoblasts. Nifedipine (L-type calcium channel blocker) did not affect the advanced glycation endproducts-induced decrease in osteoblastic proliferation, although it blocked the reversion of this effect by 10−8 M Alendronate. Both advanced glycation endproducts and Alendronate inhibited the activity of intracellular neutral phosphatases. In conclusion, we show that bisphosphonates revert the deleterious actions of advanced glycation endproducts on osteoblastic cells, and that these effects of bisphosphonates depend on: (a) Ca2+ influx through L-type voltage-sensitive channels, and (b) blockage of advanced glycation endproducts-induced reactive oxygen species generation.2008info:eu-repo/semantics/articleinfo:eu-repo/semantics/submittedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfhttps://digital.cic.gba.gob.ar/handle/11746/4760enginfo:eu-repo/semantics/openAccesshttp://creativecommons.org/licenses/by/4.0/reponame:CIC Digital (CICBA)instname:Comisión de Investigaciones Científicas de la Provincia de Buenos Airesinstacron:CICBA2025-09-29T13:40:11Zoai:digital.cic.gba.gob.ar:11746/4760Institucionalhttp://digital.cic.gba.gob.arOrganismo científico-tecnológicoNo correspondehttp://digital.cic.gba.gob.ar/oai/snrdmarisa.degiusti@sedici.unlp.edu.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:94412025-09-29 13:40:12.025CIC Digital (CICBA) - Comisión de Investigaciones Científicas de la Provincia de Buenos Airesfalse
dc.title.none.fl_str_mv Opposing effects of bisphosphonates and advanced glycation end-products on osteoblastic cells
title Opposing effects of bisphosphonates and advanced glycation end-products on osteoblastic cells
spellingShingle Opposing effects of bisphosphonates and advanced glycation end-products on osteoblastic cells
Gangoiti, María Virginia
Ciencias Químicas
Bisphosphonates
Advanced glycation endproducts
Osteoblasts
Proliferation
Reactive oxygen species
title_short Opposing effects of bisphosphonates and advanced glycation end-products on osteoblastic cells
title_full Opposing effects of bisphosphonates and advanced glycation end-products on osteoblastic cells
title_fullStr Opposing effects of bisphosphonates and advanced glycation end-products on osteoblastic cells
title_full_unstemmed Opposing effects of bisphosphonates and advanced glycation end-products on osteoblastic cells
title_sort Opposing effects of bisphosphonates and advanced glycation end-products on osteoblastic cells
dc.creator.none.fl_str_mv Gangoiti, María Virginia
Cortizo, Ana María
Arnol, Verónica
Felice, Juan Ignacio
McCarthy, Antonio Desmond
author Gangoiti, María Virginia
author_facet Gangoiti, María Virginia
Cortizo, Ana María
Arnol, Verónica
Felice, Juan Ignacio
McCarthy, Antonio Desmond
author_role author
author2 Cortizo, Ana María
Arnol, Verónica
Felice, Juan Ignacio
McCarthy, Antonio Desmond
author2_role author
author
author
author
dc.subject.none.fl_str_mv Ciencias Químicas
Bisphosphonates
Advanced glycation endproducts
Osteoblasts
Proliferation
Reactive oxygen species
topic Ciencias Químicas
Bisphosphonates
Advanced glycation endproducts
Osteoblasts
Proliferation
Reactive oxygen species
dc.description.none.fl_txt_mv Patients with long-standing Diabetes mellitus can develop osteopenia and osteoporosis. We have previously shown that advanced glycation endproducts reduce the bone-forming activity of osteoblasts. Bisphosphonates are used for the treatment of various bone disorders, since they reduce osteoclastic function and survival, and stimulate osteoblastic bone-forming capacity. In this work we have investigated whether bisphosphonates are able to revert advanced glycation endproducts-induced deleterious effects in osteoblasts. MC3T3E1 and UMR106 osteoblastic cells were incubated with control or advanced glycation endproducts-modified bovine serum albumin, in the presence or absence of different doses of the bisphosphonates Alendronate, Pamidronate or Zoledronate. After 24–72 h of culture, we evaluated their effects on cell proliferation and apoptosis, type-1 collagen production, alkaline and neutral phosphatase activity, and intracellular reactive oxygen species production. Advanced glycation endproducts significantly decreased osteoblast proliferation, alkaline phosphatase activity and type 1 collagen production, while increasing osteoblastic apoptosis and reactive oxygen species production. These effects were completely reverted by low doses (10−8 M) of bisphosphonates. High doses of bisphosphonates (10−4–10−5 M) were toxic for osteoblasts. Nifedipine (L-type calcium channel blocker) did not affect the advanced glycation endproducts-induced decrease in osteoblastic proliferation, although it blocked the reversion of this effect by 10−8 M Alendronate. Both advanced glycation endproducts and Alendronate inhibited the activity of intracellular neutral phosphatases. In conclusion, we show that bisphosphonates revert the deleterious actions of advanced glycation endproducts on osteoblastic cells, and that these effects of bisphosphonates depend on: (a) Ca2+ influx through L-type voltage-sensitive channels, and (b) blockage of advanced glycation endproducts-induced reactive oxygen species generation.
description Patients with long-standing Diabetes mellitus can develop osteopenia and osteoporosis. We have previously shown that advanced glycation endproducts reduce the bone-forming activity of osteoblasts. Bisphosphonates are used for the treatment of various bone disorders, since they reduce osteoclastic function and survival, and stimulate osteoblastic bone-forming capacity. In this work we have investigated whether bisphosphonates are able to revert advanced glycation endproducts-induced deleterious effects in osteoblasts. MC3T3E1 and UMR106 osteoblastic cells were incubated with control or advanced glycation endproducts-modified bovine serum albumin, in the presence or absence of different doses of the bisphosphonates Alendronate, Pamidronate or Zoledronate. After 24–72 h of culture, we evaluated their effects on cell proliferation and apoptosis, type-1 collagen production, alkaline and neutral phosphatase activity, and intracellular reactive oxygen species production. Advanced glycation endproducts significantly decreased osteoblast proliferation, alkaline phosphatase activity and type 1 collagen production, while increasing osteoblastic apoptosis and reactive oxygen species production. These effects were completely reverted by low doses (10−8 M) of bisphosphonates. High doses of bisphosphonates (10−4–10−5 M) were toxic for osteoblasts. Nifedipine (L-type calcium channel blocker) did not affect the advanced glycation endproducts-induced decrease in osteoblastic proliferation, although it blocked the reversion of this effect by 10−8 M Alendronate. Both advanced glycation endproducts and Alendronate inhibited the activity of intracellular neutral phosphatases. In conclusion, we show that bisphosphonates revert the deleterious actions of advanced glycation endproducts on osteoblastic cells, and that these effects of bisphosphonates depend on: (a) Ca2+ influx through L-type voltage-sensitive channels, and (b) blockage of advanced glycation endproducts-induced reactive oxygen species generation.
publishDate 2008
dc.date.none.fl_str_mv 2008
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/submittedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str submittedVersion
dc.identifier.none.fl_str_mv https://digital.cic.gba.gob.ar/handle/11746/4760
url https://digital.cic.gba.gob.ar/handle/11746/4760
dc.language.none.fl_str_mv eng
language eng
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
http://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
rights_invalid_str_mv http://creativecommons.org/licenses/by/4.0/
dc.format.none.fl_str_mv application/pdf
dc.source.none.fl_str_mv reponame:CIC Digital (CICBA)
instname:Comisión de Investigaciones Científicas de la Provincia de Buenos Aires
instacron:CICBA
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collection CIC Digital (CICBA)
instname_str Comisión de Investigaciones Científicas de la Provincia de Buenos Aires
instacron_str CICBA
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repository.name.fl_str_mv CIC Digital (CICBA) - Comisión de Investigaciones Científicas de la Provincia de Buenos Aires
repository.mail.fl_str_mv marisa.degiusti@sedici.unlp.edu.ar
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