Advanced Glycation Endproducts and Alendronate Differentially Inhibit early and Late Osteoclastogenesis In vitro

Autores
Gangoiti, María Virginia; Arnol, Verónica; Cortizo, Ana María; McCarthy, Antonio Desmond
Año de publicación
2013
Idioma
inglés
Tipo de recurso
artículo
Estado
versión enviada
Descripción
Advanced Glycation Endproducts (AGEs) are greatly elevated in bone extracellular matrix of patients with Diabetes mellitus, and this has been associated with the increased incidence of fractures observed in these patients. AGEs affect the homeostasis of bone cells such as osteoblasts and osteoclasts. Bisphosphonates are first-line anti-osteoporotic drugs that principally exert their effects by inhibiting osteoclastic activity. However, the effect of bisphosphonate treatment on bone quality in patients with Diabetes is uncertain. In the present work we have evaluated the action of AGEs (50-200 μg/ml), with or without Alendronate (10-8-10-4M), on osteoclastogenesis induced by co-cultures of Raw 264.7 macrophages and UMR106 osteoblasts. We determined the effects of different culture conditions on osteoclastic recruitment, tartrate-resistant acid phosphatase (TRAP) activity and expression of RAGE (receptor for AGEs); and on the osteoblastic expression of RANK ligand (RANKL). AGEs and Alendronate inhibited the recruitment and TRAP activity of osteoclasts, with an additive effect of both agents at high concentrations of Alendronate. While AGEs prevented the early and late stages of osteoclastogenesis, Alendronate (alone or in co-incubation with AGEs) only inhibited its later stages. In addition, both AGEs and Alendronate increased the osteoclastic expression of RAGE and decreased the osteoblastic expression of RANKL, correlating closely with their inhibition of osteoclastogenesis. If these in vitro results can be extrapolated to a clinical setting, they may be indicating a potentiation of the anti-resorptive effects of Alendronate in the context of bone extracellular matrix with excess accumulation of AGEs, as might occur in a patient with Diabetes mellitus.
Materia
Ciencias Químicas
Advanced glycation endproducts
Osteoclasts
Alendronate
RAGE
RANKL
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:11746/4864

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network_name_str CIC Digital (CICBA)
spelling Advanced Glycation Endproducts and Alendronate Differentially Inhibit early and Late Osteoclastogenesis In vitroGangoiti, María VirginiaArnol, VerónicaCortizo, Ana MaríaMcCarthy, Antonio DesmondCiencias QuímicasAdvanced glycation endproductsOsteoclastsAlendronateRAGERANKLAdvanced Glycation Endproducts (AGEs) are greatly elevated in bone extracellular matrix of patients with Diabetes mellitus, and this has been associated with the increased incidence of fractures observed in these patients. AGEs affect the homeostasis of bone cells such as osteoblasts and osteoclasts. Bisphosphonates are first-line anti-osteoporotic drugs that principally exert their effects by inhibiting osteoclastic activity. However, the effect of bisphosphonate treatment on bone quality in patients with Diabetes is uncertain. In the present work we have evaluated the action of AGEs (50-200 μg/ml), with or without Alendronate (10-8-10-4M), on osteoclastogenesis induced by co-cultures of Raw 264.7 macrophages and UMR106 osteoblasts. We determined the effects of different culture conditions on osteoclastic recruitment, tartrate-resistant acid phosphatase (TRAP) activity and expression of RAGE (receptor for AGEs); and on the osteoblastic expression of RANK ligand (RANKL). AGEs and Alendronate inhibited the recruitment and TRAP activity of osteoclasts, with an additive effect of both agents at high concentrations of Alendronate. While AGEs prevented the early and late stages of osteoclastogenesis, Alendronate (alone or in co-incubation with AGEs) only inhibited its later stages. In addition, both AGEs and Alendronate increased the osteoclastic expression of RAGE and decreased the osteoblastic expression of RANKL, correlating closely with their inhibition of osteoclastogenesis. If these in vitro results can be extrapolated to a clinical setting, they may be indicating a potentiation of the anti-resorptive effects of Alendronate in the context of bone extracellular matrix with excess accumulation of AGEs, as might occur in a patient with Diabetes mellitus.2013info: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/11746/4864enginfo:eu-repo/semantics/altIdentifier/doi/10.4172/2155-6156.1000274info:eu-repo/semantics/altIdentifier/issn/2155-6156info: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:CICBA2025-09-29T13:39:55Zoai:digital.cic.gba.gob.ar:11746/4864Institucionalhttp://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 13:39:56.084CIC Digital (CICBA) - Comisión de Investigaciones Científicas de la Provincia de Buenos Airesfalse
dc.title.none.fl_str_mv Advanced Glycation Endproducts and Alendronate Differentially Inhibit early and Late Osteoclastogenesis In vitro
title Advanced Glycation Endproducts and Alendronate Differentially Inhibit early and Late Osteoclastogenesis In vitro
spellingShingle Advanced Glycation Endproducts and Alendronate Differentially Inhibit early and Late Osteoclastogenesis In vitro
Gangoiti, María Virginia
Ciencias Químicas
Advanced glycation endproducts
Osteoclasts
Alendronate
RAGE
RANKL
title_short Advanced Glycation Endproducts and Alendronate Differentially Inhibit early and Late Osteoclastogenesis In vitro
title_full Advanced Glycation Endproducts and Alendronate Differentially Inhibit early and Late Osteoclastogenesis In vitro
title_fullStr Advanced Glycation Endproducts and Alendronate Differentially Inhibit early and Late Osteoclastogenesis In vitro
title_full_unstemmed Advanced Glycation Endproducts and Alendronate Differentially Inhibit early and Late Osteoclastogenesis In vitro
title_sort Advanced Glycation Endproducts and Alendronate Differentially Inhibit early and Late Osteoclastogenesis In vitro
dc.creator.none.fl_str_mv Gangoiti, María Virginia
Arnol, Verónica
Cortizo, Ana María
McCarthy, Antonio Desmond
author Gangoiti, María Virginia
author_facet Gangoiti, María Virginia
Arnol, Verónica
Cortizo, Ana María
McCarthy, Antonio Desmond
author_role author
author2 Arnol, Verónica
Cortizo, Ana María
McCarthy, Antonio Desmond
author2_role author
author
author
dc.subject.none.fl_str_mv Ciencias Químicas
Advanced glycation endproducts
Osteoclasts
Alendronate
RAGE
RANKL
topic Ciencias Químicas
Advanced glycation endproducts
Osteoclasts
Alendronate
RAGE
RANKL
dc.description.none.fl_txt_mv Advanced Glycation Endproducts (AGEs) are greatly elevated in bone extracellular matrix of patients with Diabetes mellitus, and this has been associated with the increased incidence of fractures observed in these patients. AGEs affect the homeostasis of bone cells such as osteoblasts and osteoclasts. Bisphosphonates are first-line anti-osteoporotic drugs that principally exert their effects by inhibiting osteoclastic activity. However, the effect of bisphosphonate treatment on bone quality in patients with Diabetes is uncertain. In the present work we have evaluated the action of AGEs (50-200 μg/ml), with or without Alendronate (10-8-10-4M), on osteoclastogenesis induced by co-cultures of Raw 264.7 macrophages and UMR106 osteoblasts. We determined the effects of different culture conditions on osteoclastic recruitment, tartrate-resistant acid phosphatase (TRAP) activity and expression of RAGE (receptor for AGEs); and on the osteoblastic expression of RANK ligand (RANKL). AGEs and Alendronate inhibited the recruitment and TRAP activity of osteoclasts, with an additive effect of both agents at high concentrations of Alendronate. While AGEs prevented the early and late stages of osteoclastogenesis, Alendronate (alone or in co-incubation with AGEs) only inhibited its later stages. In addition, both AGEs and Alendronate increased the osteoclastic expression of RAGE and decreased the osteoblastic expression of RANKL, correlating closely with their inhibition of osteoclastogenesis. If these in vitro results can be extrapolated to a clinical setting, they may be indicating a potentiation of the anti-resorptive effects of Alendronate in the context of bone extracellular matrix with excess accumulation of AGEs, as might occur in a patient with Diabetes mellitus.
description Advanced Glycation Endproducts (AGEs) are greatly elevated in bone extracellular matrix of patients with Diabetes mellitus, and this has been associated with the increased incidence of fractures observed in these patients. AGEs affect the homeostasis of bone cells such as osteoblasts and osteoclasts. Bisphosphonates are first-line anti-osteoporotic drugs that principally exert their effects by inhibiting osteoclastic activity. However, the effect of bisphosphonate treatment on bone quality in patients with Diabetes is uncertain. In the present work we have evaluated the action of AGEs (50-200 μg/ml), with or without Alendronate (10-8-10-4M), on osteoclastogenesis induced by co-cultures of Raw 264.7 macrophages and UMR106 osteoblasts. We determined the effects of different culture conditions on osteoclastic recruitment, tartrate-resistant acid phosphatase (TRAP) activity and expression of RAGE (receptor for AGEs); and on the osteoblastic expression of RANK ligand (RANKL). AGEs and Alendronate inhibited the recruitment and TRAP activity of osteoclasts, with an additive effect of both agents at high concentrations of Alendronate. While AGEs prevented the early and late stages of osteoclastogenesis, Alendronate (alone or in co-incubation with AGEs) only inhibited its later stages. In addition, both AGEs and Alendronate increased the osteoclastic expression of RAGE and decreased the osteoblastic expression of RANKL, correlating closely with their inhibition of osteoclastogenesis. If these in vitro results can be extrapolated to a clinical setting, they may be indicating a potentiation of the anti-resorptive effects of Alendronate in the context of bone extracellular matrix with excess accumulation of AGEs, as might occur in a patient with Diabetes mellitus.
publishDate 2013
dc.date.none.fl_str_mv 2013
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dc.identifier.none.fl_str_mv https://digital.cic.gba.gob.ar/handle/11746/4864
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language eng
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info:eu-repo/semantics/altIdentifier/issn/2155-6156
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