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Vanadate Impedes Adipogenesis in Mesenchymal Stem Cells Derived from Different Depots within Bone

Glucocorticoid-induced osteoporosis (GIO) is associated with an increase in bone marrow adiposity, which skews the differentiation of mesenchymal stem cell (MSC) progenitors away from osteoblastogenesis and toward adipogenesis. We have previously found that vanadate, a non-specific protein tyrosine...

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Autores principales: Jacobs, Frans Alexander, Sadie-Van Gijsen, Hanél, van de Vyver, Mari, Ferris, William Frank
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4971437/
https://www.ncbi.nlm.nih.gov/pubmed/27536268
http://dx.doi.org/10.3389/fendo.2016.00108
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author Jacobs, Frans Alexander
Sadie-Van Gijsen, Hanél
van de Vyver, Mari
Ferris, William Frank
author_facet Jacobs, Frans Alexander
Sadie-Van Gijsen, Hanél
van de Vyver, Mari
Ferris, William Frank
author_sort Jacobs, Frans Alexander
collection PubMed
description Glucocorticoid-induced osteoporosis (GIO) is associated with an increase in bone marrow adiposity, which skews the differentiation of mesenchymal stem cell (MSC) progenitors away from osteoblastogenesis and toward adipogenesis. We have previously found that vanadate, a non-specific protein tyrosine phosphatase inhibitor, prevents GIO in rats, but it was unclear whether vanadate directly influenced adipogenesis in bone-derived MSCs. For the present study, we investigated the effect of vanadate on adipogenesis in primary rat MSCs derived from bone marrow (bmMSCs) and from the proximal end of the femur (pfMSCs). By passage 3 after isolation, both cell populations expressed the MSC cell surface markers CD90 and CD106, but not the hematopoietic marker CD45. However, although variable, expression of the fibroblast marker CD26 was higher in pfMSCs than in bmMSCs. Differentiation studies using osteogenic and adipogenic induction media (OM and AM, respectively) demonstrated that pfMSCs rapidly accumulated lipid droplets within 1 week of exposure to AM, while bmMSCs isolated from the same femur only formed lipid droplets after 3 weeks of AM treatment. Conversely, pfMSCs exposed to OM produced mineralized extracellular matrix (ECM) after 3 weeks, compared to 1 week for OM-treated bmMSCs. Vanadate (10 μM) added to AM resulted in a significant reduction in AM-induced intracellular lipid accumulation and expression of adipogenic gene markers (PPARγ2, aP2, adipsin) in both pfMSCs and bmMSCs. Pharmacological concentrations of glucocorticoids (1 μM) alone did not induce lipid accumulation in either bmMSCs or pfMSCs, but resulted in significant cell death in pfMSCs. Our findings demonstrate the existence of at least two fundamentally different MSC depots within the femur and highlights the presence of MSCs capable of rapid adipogenesis within the proximal femur, an area prone to osteoporotic fractures. In addition, our results suggest that the increased bone marrow adiposity observed in GIO may not be solely due to direct effect of glucocorticoids on bone-derived MSCs, and that an increase in femur lipid content may also arise from increased adipogenesis in MSCs residing outside of the bone marrow niche.
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spelling pubmed-49714372016-08-17 Vanadate Impedes Adipogenesis in Mesenchymal Stem Cells Derived from Different Depots within Bone Jacobs, Frans Alexander Sadie-Van Gijsen, Hanél van de Vyver, Mari Ferris, William Frank Front Endocrinol (Lausanne) Endocrinology Glucocorticoid-induced osteoporosis (GIO) is associated with an increase in bone marrow adiposity, which skews the differentiation of mesenchymal stem cell (MSC) progenitors away from osteoblastogenesis and toward adipogenesis. We have previously found that vanadate, a non-specific protein tyrosine phosphatase inhibitor, prevents GIO in rats, but it was unclear whether vanadate directly influenced adipogenesis in bone-derived MSCs. For the present study, we investigated the effect of vanadate on adipogenesis in primary rat MSCs derived from bone marrow (bmMSCs) and from the proximal end of the femur (pfMSCs). By passage 3 after isolation, both cell populations expressed the MSC cell surface markers CD90 and CD106, but not the hematopoietic marker CD45. However, although variable, expression of the fibroblast marker CD26 was higher in pfMSCs than in bmMSCs. Differentiation studies using osteogenic and adipogenic induction media (OM and AM, respectively) demonstrated that pfMSCs rapidly accumulated lipid droplets within 1 week of exposure to AM, while bmMSCs isolated from the same femur only formed lipid droplets after 3 weeks of AM treatment. Conversely, pfMSCs exposed to OM produced mineralized extracellular matrix (ECM) after 3 weeks, compared to 1 week for OM-treated bmMSCs. Vanadate (10 μM) added to AM resulted in a significant reduction in AM-induced intracellular lipid accumulation and expression of adipogenic gene markers (PPARγ2, aP2, adipsin) in both pfMSCs and bmMSCs. Pharmacological concentrations of glucocorticoids (1 μM) alone did not induce lipid accumulation in either bmMSCs or pfMSCs, but resulted in significant cell death in pfMSCs. Our findings demonstrate the existence of at least two fundamentally different MSC depots within the femur and highlights the presence of MSCs capable of rapid adipogenesis within the proximal femur, an area prone to osteoporotic fractures. In addition, our results suggest that the increased bone marrow adiposity observed in GIO may not be solely due to direct effect of glucocorticoids on bone-derived MSCs, and that an increase in femur lipid content may also arise from increased adipogenesis in MSCs residing outside of the bone marrow niche. Frontiers Media S.A. 2016-08-03 /pmc/articles/PMC4971437/ /pubmed/27536268 http://dx.doi.org/10.3389/fendo.2016.00108 Text en Copyright © 2016 Jacobs, Sadie-Van Gijsen, van de Vyver and Ferris. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Endocrinology
Jacobs, Frans Alexander
Sadie-Van Gijsen, Hanél
van de Vyver, Mari
Ferris, William Frank
Vanadate Impedes Adipogenesis in Mesenchymal Stem Cells Derived from Different Depots within Bone
title Vanadate Impedes Adipogenesis in Mesenchymal Stem Cells Derived from Different Depots within Bone
title_full Vanadate Impedes Adipogenesis in Mesenchymal Stem Cells Derived from Different Depots within Bone
title_fullStr Vanadate Impedes Adipogenesis in Mesenchymal Stem Cells Derived from Different Depots within Bone
title_full_unstemmed Vanadate Impedes Adipogenesis in Mesenchymal Stem Cells Derived from Different Depots within Bone
title_short Vanadate Impedes Adipogenesis in Mesenchymal Stem Cells Derived from Different Depots within Bone
title_sort vanadate impedes adipogenesis in mesenchymal stem cells derived from different depots within bone
topic Endocrinology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4971437/
https://www.ncbi.nlm.nih.gov/pubmed/27536268
http://dx.doi.org/10.3389/fendo.2016.00108
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