Saxagliptin affects long-bone microarchitecture and decreases the osteogenic potential of bone marrow stromal cells

Autores
Sbaraglini, Maria Laura; Molinuevo, María Silvina; Sedlinsky, Claudia; Schurman, León; McCarthy, Antonio Desmond
Año de publicación
2014
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Diabetes mellitus is associated with a decrease in bone quality and an increase in fracture incidence. Additionally, treatment with anti-diabetic drugs can either adversely or positively affect bone metabo- lism. In this study we evaluated: the effect of a 3-week oral treatment with saxagliptin on femoral microarchitecture in young male non-type-2-diabetic Sprague Dawley rats; and the in vitro effect of saxagliptin and/or fetal bovine serum (FBS), insulin or insulin-like growth factor-1 (IGF1), on the proliferation, differentiation (Runx2 and PPAR-gamma expression, type-1 collagen production, osteo- calcin expression, mineralization) and extracellular-regulated kinase (ERK) activation, in bone marrow stromal cells (MSC) obtained from control (untreated) rats and in MC3T3E1 osteoblast-like cells. In vivo, oral saxagliptin treatment induced a significant decrease in the femoral osteocytic and osteoblastic density of metaphyseal trabecular bone and in the average height of the proximal cartilage growth plate; and an increase in osteoclastic tartrate-resistant acid phosphatase (TRAP) activity of the primary spongiosa. In vitro, saxagliptin inhibited FBS-, insulin- and IGF1-induced ERK phosphorylation and cell proliferation, in both MSC and MC3T3E1 preosteoblasts. In the absence of growth factors, saxagliptin had no effect on ERK activation or cell proliferation. In both MSC and MC3T3E1 cells, saxagliptin in the presence of FBS inhibited Runx2 and osteocalcin expression, type-1 collagen production and miner- alization, while increasing PPAR-gamma expression. In conclusion, orally administered saxagliptin induced alterations in long-bone microarchitecture that could be related to its in vitro down- regulation of the ERK signaling pathway for insulin and IGF1 in MSC, thus decreasing the osteogenic potential of these cells.
Fil: Sbaraglini, Maria Laura. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Departamento de Ciencias Biológicas. Laboratorio de Investigación en Osteospatías y Metabolismo Mineral; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Molinuevo, María Silvina. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Departamento de Ciencias Biológicas. Laboratorio de Investigación en Osteospatías y Metabolismo Mineral; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Sedlinsky, Claudia. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Departamento de Ciencias Biológicas. Laboratorio de Investigación en Osteospatías y Metabolismo Mineral; Argentina
Fil: Schurman, León. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Departamento de Ciencias Biológicas. Laboratorio de Investigación en Osteospatías y Metabolismo Mineral; Argentina
Fil: McCarthy, Antonio Desmond. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Departamento de Ciencias Biológicas. Laboratorio de Investigación en Osteospatías y Metabolismo Mineral; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Materia
Bone Microarchitecture
Diabetes Mellitus
Saxagliptin
Dipeptidyl-Peptidase 4
Osteoblastsbone Marrow Stromal Cells
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/24631
Acceder
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network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Saxagliptin affects long-bone microarchitecture and decreases the osteogenic potential of bone marrow stromal cellsSbaraglini, Maria LauraMolinuevo, María SilvinaSedlinsky, ClaudiaSchurman, LeónMcCarthy, Antonio DesmondBone MicroarchitectureDiabetes MellitusSaxagliptinDipeptidyl-Peptidase 4Osteoblastsbone Marrow Stromal Cellshttps://purl.org/becyt/ford/3.3https://purl.org/becyt/ford/3Diabetes mellitus is associated with a decrease in bone quality and an increase in fracture incidence. Additionally, treatment with anti-diabetic drugs can either adversely or positively affect bone metabo- lism. In this study we evaluated: the effect of a 3-week oral treatment with saxagliptin on femoral microarchitecture in young male non-type-2-diabetic Sprague Dawley rats; and the in vitro effect of saxagliptin and/or fetal bovine serum (FBS), insulin or insulin-like growth factor-1 (IGF1), on the proliferation, differentiation (Runx2 and PPAR-gamma expression, type-1 collagen production, osteo- calcin expression, mineralization) and extracellular-regulated kinase (ERK) activation, in bone marrow stromal cells (MSC) obtained from control (untreated) rats and in MC3T3E1 osteoblast-like cells. In vivo, oral saxagliptin treatment induced a significant decrease in the femoral osteocytic and osteoblastic density of metaphyseal trabecular bone and in the average height of the proximal cartilage growth plate; and an increase in osteoclastic tartrate-resistant acid phosphatase (TRAP) activity of the primary spongiosa. In vitro, saxagliptin inhibited FBS-, insulin- and IGF1-induced ERK phosphorylation and cell proliferation, in both MSC and MC3T3E1 preosteoblasts. In the absence of growth factors, saxagliptin had no effect on ERK activation or cell proliferation. In both MSC and MC3T3E1 cells, saxagliptin in the presence of FBS inhibited Runx2 and osteocalcin expression, type-1 collagen production and miner- alization, while increasing PPAR-gamma expression. In conclusion, orally administered saxagliptin induced alterations in long-bone microarchitecture that could be related to its in vitro down- regulation of the ERK signaling pathway for insulin and IGF1 in MSC, thus decreasing the osteogenic potential of these cells.Fil: Sbaraglini, Maria Laura. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Departamento de Ciencias Biológicas. Laboratorio de Investigación en Osteospatías y Metabolismo Mineral; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Molinuevo, María Silvina. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Departamento de Ciencias Biológicas. Laboratorio de Investigación en Osteospatías y Metabolismo Mineral; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Sedlinsky, Claudia. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Departamento de Ciencias Biológicas. Laboratorio de Investigación en Osteospatías y Metabolismo Mineral; ArgentinaFil: Schurman, León. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Departamento de Ciencias Biológicas. Laboratorio de Investigación en Osteospatías y Metabolismo Mineral; ArgentinaFil: McCarthy, Antonio Desmond. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Departamento de Ciencias Biológicas. Laboratorio de Investigación en Osteospatías y Metabolismo Mineral; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaElsevier Science2014-03-15info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/24631Sbaraglini, Maria Laura; Molinuevo, María Silvina; Sedlinsky, Claudia; Schurman, León; McCarthy, Antonio Desmond; Saxagliptin affects long-bone microarchitecture and decreases the osteogenic potential of bone marrow stromal cells; Elsevier Science; European Journal of Pharmacology; 727; 15-3-2014; 8-140014-2999CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1016/j.ejphar.2014.01.028info:eu-repo/semantics/altIdentifier/url/http://linkinghub.elsevier.com/retrieve/pii/S0014299914000478info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-15T15:33:59Zoai:ri.conicet.gov.ar:11336/24631instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-10-15 15:33:59.678CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Saxagliptin affects long-bone microarchitecture and decreases the osteogenic potential of bone marrow stromal cells
title Saxagliptin affects long-bone microarchitecture and decreases the osteogenic potential of bone marrow stromal cells
spellingShingle Saxagliptin affects long-bone microarchitecture and decreases the osteogenic potential of bone marrow stromal cells
Sbaraglini, Maria Laura
Bone Microarchitecture
Diabetes Mellitus
Saxagliptin
Dipeptidyl-Peptidase 4
Osteoblastsbone Marrow Stromal Cells
title_short Saxagliptin affects long-bone microarchitecture and decreases the osteogenic potential of bone marrow stromal cells
title_full Saxagliptin affects long-bone microarchitecture and decreases the osteogenic potential of bone marrow stromal cells
title_fullStr Saxagliptin affects long-bone microarchitecture and decreases the osteogenic potential of bone marrow stromal cells
title_full_unstemmed Saxagliptin affects long-bone microarchitecture and decreases the osteogenic potential of bone marrow stromal cells
title_sort Saxagliptin affects long-bone microarchitecture and decreases the osteogenic potential of bone marrow stromal cells
dc.creator.none.fl_str_mv Sbaraglini, Maria Laura
Molinuevo, María Silvina
Sedlinsky, Claudia
Schurman, León
McCarthy, Antonio Desmond
author Sbaraglini, Maria Laura
author_facet Sbaraglini, Maria Laura
Molinuevo, María Silvina
Sedlinsky, Claudia
Schurman, León
McCarthy, Antonio Desmond
author_role author
author2 Molinuevo, María Silvina
Sedlinsky, Claudia
Schurman, León
McCarthy, Antonio Desmond
author2_role author
author
author
author
dc.subject.none.fl_str_mv Bone Microarchitecture
Diabetes Mellitus
Saxagliptin
Dipeptidyl-Peptidase 4
Osteoblastsbone Marrow Stromal Cells
topic Bone Microarchitecture
Diabetes Mellitus
Saxagliptin
Dipeptidyl-Peptidase 4
Osteoblastsbone Marrow Stromal Cells
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.3
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Diabetes mellitus is associated with a decrease in bone quality and an increase in fracture incidence. Additionally, treatment with anti-diabetic drugs can either adversely or positively affect bone metabo- lism. In this study we evaluated: the effect of a 3-week oral treatment with saxagliptin on femoral microarchitecture in young male non-type-2-diabetic Sprague Dawley rats; and the in vitro effect of saxagliptin and/or fetal bovine serum (FBS), insulin or insulin-like growth factor-1 (IGF1), on the proliferation, differentiation (Runx2 and PPAR-gamma expression, type-1 collagen production, osteo- calcin expression, mineralization) and extracellular-regulated kinase (ERK) activation, in bone marrow stromal cells (MSC) obtained from control (untreated) rats and in MC3T3E1 osteoblast-like cells. In vivo, oral saxagliptin treatment induced a significant decrease in the femoral osteocytic and osteoblastic density of metaphyseal trabecular bone and in the average height of the proximal cartilage growth plate; and an increase in osteoclastic tartrate-resistant acid phosphatase (TRAP) activity of the primary spongiosa. In vitro, saxagliptin inhibited FBS-, insulin- and IGF1-induced ERK phosphorylation and cell proliferation, in both MSC and MC3T3E1 preosteoblasts. In the absence of growth factors, saxagliptin had no effect on ERK activation or cell proliferation. In both MSC and MC3T3E1 cells, saxagliptin in the presence of FBS inhibited Runx2 and osteocalcin expression, type-1 collagen production and miner- alization, while increasing PPAR-gamma expression. In conclusion, orally administered saxagliptin induced alterations in long-bone microarchitecture that could be related to its in vitro down- regulation of the ERK signaling pathway for insulin and IGF1 in MSC, thus decreasing the osteogenic potential of these cells.
Fil: Sbaraglini, Maria Laura. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Departamento de Ciencias Biológicas. Laboratorio de Investigación en Osteospatías y Metabolismo Mineral; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Molinuevo, María Silvina. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Departamento de Ciencias Biológicas. Laboratorio de Investigación en Osteospatías y Metabolismo Mineral; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Sedlinsky, Claudia. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Departamento de Ciencias Biológicas. Laboratorio de Investigación en Osteospatías y Metabolismo Mineral; Argentina
Fil: Schurman, León. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Departamento de Ciencias Biológicas. Laboratorio de Investigación en Osteospatías y Metabolismo Mineral; Argentina
Fil: McCarthy, Antonio Desmond. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Departamento de Ciencias Biológicas. Laboratorio de Investigación en Osteospatías y Metabolismo Mineral; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
description Diabetes mellitus is associated with a decrease in bone quality and an increase in fracture incidence. Additionally, treatment with anti-diabetic drugs can either adversely or positively affect bone metabo- lism. In this study we evaluated: the effect of a 3-week oral treatment with saxagliptin on femoral microarchitecture in young male non-type-2-diabetic Sprague Dawley rats; and the in vitro effect of saxagliptin and/or fetal bovine serum (FBS), insulin or insulin-like growth factor-1 (IGF1), on the proliferation, differentiation (Runx2 and PPAR-gamma expression, type-1 collagen production, osteo- calcin expression, mineralization) and extracellular-regulated kinase (ERK) activation, in bone marrow stromal cells (MSC) obtained from control (untreated) rats and in MC3T3E1 osteoblast-like cells. In vivo, oral saxagliptin treatment induced a significant decrease in the femoral osteocytic and osteoblastic density of metaphyseal trabecular bone and in the average height of the proximal cartilage growth plate; and an increase in osteoclastic tartrate-resistant acid phosphatase (TRAP) activity of the primary spongiosa. In vitro, saxagliptin inhibited FBS-, insulin- and IGF1-induced ERK phosphorylation and cell proliferation, in both MSC and MC3T3E1 preosteoblasts. In the absence of growth factors, saxagliptin had no effect on ERK activation or cell proliferation. In both MSC and MC3T3E1 cells, saxagliptin in the presence of FBS inhibited Runx2 and osteocalcin expression, type-1 collagen production and miner- alization, while increasing PPAR-gamma expression. In conclusion, orally administered saxagliptin induced alterations in long-bone microarchitecture that could be related to its in vitro down- regulation of the ERK signaling pathway for insulin and IGF1 in MSC, thus decreasing the osteogenic potential of these cells.
publishDate 2014
dc.date.none.fl_str_mv 2014-03-15
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/24631
Sbaraglini, Maria Laura; Molinuevo, María Silvina; Sedlinsky, Claudia; Schurman, León; McCarthy, Antonio Desmond; Saxagliptin affects long-bone microarchitecture and decreases the osteogenic potential of bone marrow stromal cells; Elsevier Science; European Journal of Pharmacology; 727; 15-3-2014; 8-14
0014-2999
CONICET Digital
CONICET
url http://hdl.handle.net/11336/24631
identifier_str_mv Sbaraglini, Maria Laura; Molinuevo, María Silvina; Sedlinsky, Claudia; Schurman, León; McCarthy, Antonio Desmond; Saxagliptin affects long-bone microarchitecture and decreases the osteogenic potential of bone marrow stromal cells; Elsevier Science; European Journal of Pharmacology; 727; 15-3-2014; 8-14
0014-2999
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1016/j.ejphar.2014.01.028
info:eu-repo/semantics/altIdentifier/url/http://linkinghub.elsevier.com/retrieve/pii/S0014299914000478
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv Elsevier Science
publisher.none.fl_str_mv Elsevier Science
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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