Alendronate Can Improve Bone Alterations in Experimental Diabetes by Preventing Antiosteogenic, Antichondrogenic, and Proadipocytic Effects of AGEs on Bone Marrow Progenitor Cells

Bisphosphonates such as alendronate are antiosteoporotic drugs that inhibit the activity of bone-resorbing osteoclasts and secondarily promote osteoblastic function. Diabetes increases bone-matrix-associated advanced glycation end products (AGEs) that impair bone marrow progenitor cell (BMPC) osteog...

Descripción completa

Detalles Bibliográficos
Autores principales: Chuguransky, Sara Rocío, Cortizo, Ana María, McCarthy, Antonio Desmond
Formato: Articulo
Lenguaje:Inglés
Publicado: 2016
Materias:
Acceso en línea:http://sedici.unlp.edu.ar/handle/10915/85731
Aporte de:
id I19-R120-10915-85731
record_format dspace
institution Universidad Nacional de La Plata
institution_str I-19
repository_str R-120
collection SEDICI (UNLP)
language Inglés
topic Ciencias Exactas
spellingShingle Ciencias Exactas
Chuguransky, Sara Rocío
Cortizo, Ana María
McCarthy, Antonio Desmond
Alendronate Can Improve Bone Alterations in Experimental Diabetes by Preventing Antiosteogenic, Antichondrogenic, and Proadipocytic Effects of AGEs on Bone Marrow Progenitor Cells
topic_facet Ciencias Exactas
description Bisphosphonates such as alendronate are antiosteoporotic drugs that inhibit the activity of bone-resorbing osteoclasts and secondarily promote osteoblastic function. Diabetes increases bone-matrix-associated advanced glycation end products (AGEs) that impair bone marrow progenitor cell (BMPC) osteogenic potential and decrease bone quality. Here we investigated the in vitro effect of alendronate and/or AGEs on the osteoblastogenic, adipogenic, and chondrogenic potential of BMPC isolated from nondiabetic untreated rats. We also evaluated the in vivo effect of alendronate (administered orally to rats with insulin-deficient Diabetes) on long-bone microarchitecture and BMPC multilineage potential. In vitro, the osteogenesis (Runx2, alkaline phosphatase, type 1 collagen, and mineralization) and chondrogenesis (glycosaminoglycan production) of BMPC were both decreased by AGEs, while coincubation with alendronate prevented these effects. The adipogenesis of BMPC (PPARγ, intracellular triglycerides, and lipase) was increased by AGEs, and this was prevented by coincubation with alendronate. In vivo, experimental Diabetes (a) decreased femoral trabecular bone area, osteocyte density, and osteoclastic TRAP activity; (b) increased bone marrow adiposity; and (c) deregulated BMPC phenotypic potential (increasing adipogenesis and decreasing osteogenesis and chondrogenesis). Orally administered alendronate prevented all these Diabetes-induced effects on bone. Thus, alendronate could improve bone alterations in diabetic rats by preventing the antiosteogenic, antichondrogenic, and proadipocytic effects of AGEs on BMPC.
format Articulo
Articulo
author Chuguransky, Sara Rocío
Cortizo, Ana María
McCarthy, Antonio Desmond
author_facet Chuguransky, Sara Rocío
Cortizo, Ana María
McCarthy, Antonio Desmond
author_sort Chuguransky, Sara Rocío
title Alendronate Can Improve Bone Alterations in Experimental Diabetes by Preventing Antiosteogenic, Antichondrogenic, and Proadipocytic Effects of AGEs on Bone Marrow Progenitor Cells
title_short Alendronate Can Improve Bone Alterations in Experimental Diabetes by Preventing Antiosteogenic, Antichondrogenic, and Proadipocytic Effects of AGEs on Bone Marrow Progenitor Cells
title_full Alendronate Can Improve Bone Alterations in Experimental Diabetes by Preventing Antiosteogenic, Antichondrogenic, and Proadipocytic Effects of AGEs on Bone Marrow Progenitor Cells
title_fullStr Alendronate Can Improve Bone Alterations in Experimental Diabetes by Preventing Antiosteogenic, Antichondrogenic, and Proadipocytic Effects of AGEs on Bone Marrow Progenitor Cells
title_full_unstemmed Alendronate Can Improve Bone Alterations in Experimental Diabetes by Preventing Antiosteogenic, Antichondrogenic, and Proadipocytic Effects of AGEs on Bone Marrow Progenitor Cells
title_sort alendronate can improve bone alterations in experimental diabetes by preventing antiosteogenic, antichondrogenic, and proadipocytic effects of ages on bone marrow progenitor cells
publishDate 2016
url http://sedici.unlp.edu.ar/handle/10915/85731
work_keys_str_mv AT chuguranskysararocio alendronatecanimprovebonealterationsinexperimentaldiabetesbypreventingantiosteogenicantichondrogenicandproadipocyticeffectsofagesonbonemarrowprogenitorcells
AT cortizoanamaria alendronatecanimprovebonealterationsinexperimentaldiabetesbypreventingantiosteogenicantichondrogenicandproadipocyticeffectsofagesonbonemarrowprogenitorcells
AT mccarthyantoniodesmond alendronatecanimprovebonealterationsinexperimentaldiabetesbypreventingantiosteogenicantichondrogenicandproadipocyticeffectsofagesonbonemarrowprogenitorcells
bdutipo_str Repositorios
_version_ 1764820488805154816