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
- Institución
- Comisión de Investigaciones Científicas de la Provincia de Buenos Aires
- OAI Identificador
- oai:digital.cic.gba.gob.ar:11746/4864
Ver los metadatos del registro completo
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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 |
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/11746/4864 |
url |
https://digital.cic.gba.gob.ar/handle/11746/4864 |
dc.language.none.fl_str_mv |
eng |
language |
eng |
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info:eu-repo/semantics/altIdentifier/doi/10.4172/2155-6156.1000274 info:eu-repo/semantics/altIdentifier/issn/2155-6156 |
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http://creativecommons.org/licenses/by/4.0/ |
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