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

Autores
Sbaraglini, María 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 metabolism. 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, osteocalcin 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 mineralization, 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.
Laboratorio de Investigación en Osteopatías y Metabolismo Mineral
Materia
Farmacia
Ciencias Exactas
Bone microarchitecture
Diabetes mellitus
Saxagliptin
Dipeptidyl-peptidase 4
Osteoblasts
Bone marrow stromal cells
Nivel de accesibilidad
acceso abierto
Condiciones de uso
http://creativecommons.org/licenses/by/4.0/
Repositorio
SEDICI (UNLP)
Institución
Universidad Nacional de La Plata
OAI Identificador
oai:sedici.unlp.edu.ar:10915/134104

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network_name_str SEDICI (UNLP)
spelling Saxagliptin affects long-bone microarchitecture and decreases the osteogenic potential of bone marrow stromal cellsSbaraglini, María LauraMolinuevo, María SilvinaSedlinsky, ClaudiaSchurman, LeónMcCarthy, Antonio DesmondFarmaciaCiencias ExactasBone microarchitectureDiabetes mellitusSaxagliptinDipeptidyl-peptidase 4OsteoblastsBone marrow stromal cellsDiabetes 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 metabolism. 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, osteocalcin 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 mineralization, 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.Laboratorio de Investigación en Osteopatías y Metabolismo Mineral2014-01-28info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionArticulohttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdf8-14http://sedici.unlp.edu.ar/handle/10915/134104enginfo:eu-repo/semantics/altIdentifier/issn/1879-0712info:eu-repo/semantics/altIdentifier/issn/0014-2999info:eu-repo/semantics/altIdentifier/doi/10.1016/j.ejphar.2014.01.028info:eu-repo/semantics/altIdentifier/pmid/24485890info:eu-repo/semantics/openAccesshttp://creativecommons.org/licenses/by/4.0/Creative Commons Attribution 4.0 International (CC BY 4.0)reponame:SEDICI (UNLP)instname:Universidad Nacional de La Platainstacron:UNLP2025-09-03T11:03:58Zoai:sedici.unlp.edu.ar:10915/134104Institucionalhttp://sedici.unlp.edu.ar/Universidad públicaNo correspondehttp://sedici.unlp.edu.ar/oai/snrdalira@sedici.unlp.edu.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:13292025-09-03 11:03:58.42SEDICI (UNLP) - Universidad Nacional de La Platafalse
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, María Laura
Farmacia
Ciencias Exactas
Bone microarchitecture
Diabetes mellitus
Saxagliptin
Dipeptidyl-peptidase 4
Osteoblasts
Bone 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, María Laura
Molinuevo, María Silvina
Sedlinsky, Claudia
Schurman, León
McCarthy, Antonio Desmond
author Sbaraglini, María Laura
author_facet Sbaraglini, María 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 Farmacia
Ciencias Exactas
Bone microarchitecture
Diabetes mellitus
Saxagliptin
Dipeptidyl-peptidase 4
Osteoblasts
Bone marrow stromal cells
topic Farmacia
Ciencias Exactas
Bone microarchitecture
Diabetes mellitus
Saxagliptin
Dipeptidyl-peptidase 4
Osteoblasts
Bone marrow stromal cells
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 metabolism. 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, osteocalcin 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 mineralization, 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.
Laboratorio de Investigación en Osteopatías y Metabolismo Mineral
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 metabolism. 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, osteocalcin 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 mineralization, 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 2014-01-28
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
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info:eu-repo/semantics/altIdentifier/issn/0014-2999
info:eu-repo/semantics/altIdentifier/doi/10.1016/j.ejphar.2014.01.028
info:eu-repo/semantics/altIdentifier/pmid/24485890
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
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Creative Commons Attribution 4.0 International (CC BY 4.0)
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Creative Commons Attribution 4.0 International (CC BY 4.0)
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