Advanced Glycation Endproducts and Alendronate Differentially Inhibit Early and Late Osteoclastogenesis <i>in vitro</i>

Autores
Gangoiti, María Virginia; Arnol, Verónica; Cortizo, Ana María; McCarthy, Antonio Desmond
Año de publicación
2013
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
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.
Laboratorio de Investigación en Osteopatías y Metabolismo Mineral
Materia
Ciencias Médicas
Advanced glycation endproducts
Osteoclasts
Alendronate
Rage
Rankl
Nivel de accesibilidad
acceso abierto
Condiciones de uso
http://creativecommons.org/licenses/by-nc-sa/4.0/
Repositorio
SEDICI (UNLP)
Institución
Universidad Nacional de La Plata
OAI Identificador
oai:sedici.unlp.edu.ar:10915/98429

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spelling Advanced Glycation Endproducts and Alendronate Differentially Inhibit Early and Late Osteoclastogenesis <i>in vitro</i>Gangoiti, María VirginiaArnol, VerónicaCortizo, Ana MaríaMcCarthy, Antonio DesmondCiencias MédicasAdvanced 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.Laboratorio de Investigación en Osteopatías y Metabolismo Mineral2013-07info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionArticulohttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfhttp://sedici.unlp.edu.ar/handle/10915/98429enginfo:eu-repo/semantics/altIdentifier/url/https://ri.conicet.gov.ar/11336/23956info:eu-repo/semantics/altIdentifier/issn/2155-6156info:eu-repo/semantics/altIdentifier/doi/10.4172/2155-6156.1000274info:eu-repo/semantics/altIdentifier/hdl/11336/23956info:eu-repo/semantics/openAccesshttp://creativecommons.org/licenses/by-nc-sa/4.0/Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0)reponame:SEDICI (UNLP)instname:Universidad Nacional de La Platainstacron:UNLP2025-09-29T11:20:00Zoai:sedici.unlp.edu.ar:10915/98429Institucionalhttp://sedici.unlp.edu.ar/Universidad públicaNo correspondehttp://sedici.unlp.edu.ar/oai/snrdalira@sedici.unlp.edu.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:13292025-09-29 11:20:00.988SEDICI (UNLP) - Universidad Nacional de La Platafalse
dc.title.none.fl_str_mv Advanced Glycation Endproducts and Alendronate Differentially Inhibit Early and Late Osteoclastogenesis <i>in vitro</i>
title Advanced Glycation Endproducts and Alendronate Differentially Inhibit Early and Late Osteoclastogenesis <i>in vitro</i>
spellingShingle Advanced Glycation Endproducts and Alendronate Differentially Inhibit Early and Late Osteoclastogenesis <i>in vitro</i>
Gangoiti, María Virginia
Ciencias Médicas
Advanced glycation endproducts
Osteoclasts
Alendronate
Rage
Rankl
title_short Advanced Glycation Endproducts and Alendronate Differentially Inhibit Early and Late Osteoclastogenesis <i>in vitro</i>
title_full Advanced Glycation Endproducts and Alendronate Differentially Inhibit Early and Late Osteoclastogenesis <i>in vitro</i>
title_fullStr Advanced Glycation Endproducts and Alendronate Differentially Inhibit Early and Late Osteoclastogenesis <i>in vitro</i>
title_full_unstemmed Advanced Glycation Endproducts and Alendronate Differentially Inhibit Early and Late Osteoclastogenesis <i>in vitro</i>
title_sort Advanced Glycation Endproducts and Alendronate Differentially Inhibit Early and Late Osteoclastogenesis <i>in vitro</i>
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 Médicas
Advanced glycation endproducts
Osteoclasts
Alendronate
Rage
Rankl
topic Ciencias Médicas
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.
Laboratorio de Investigación en Osteopatías y Metabolismo Mineral
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 2013-07
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info:eu-repo/semantics/publishedVersion
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status_str publishedVersion
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info:eu-repo/semantics/altIdentifier/doi/10.4172/2155-6156.1000274
info:eu-repo/semantics/altIdentifier/hdl/11336/23956
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