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
- Institución
- Universidad Nacional de La Plata
- OAI Identificador
- oai:sedici.unlp.edu.ar:10915/98429
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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 |
dc.type.none.fl_str_mv |
info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion Articulo http://purl.org/coar/resource_type/c_6501 info:ar-repo/semantics/articulo |
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http://sedici.unlp.edu.ar/handle/10915/98429 |
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http://sedici.unlp.edu.ar/handle/10915/98429 |
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eng |
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eng |
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openAccess |
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http://creativecommons.org/licenses/by-nc-sa/4.0/ Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0) |
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