How osteogenic is dexamethasone?—effect of the corticosteroid on the osteogenesis, extracellular matrix, and secretion of osteoclastogenic factors of jaw periosteum-derived mesenchymal stem/stromal cells

Dexamethasone (dexa) is commonly used to stimulate osteogenic differentiation of mesenchymal stem/stromal cells (MSCs) in vitro. However, it is paradoxical that glucocorticoids (GCs) such as dexa lead to bone loss and increased fracture risk in patients undergoing glucocorticoid therapy, causing glu...

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Main Authors: Felix Umrath, Achim Pfeifer, Wanjing Cen, Marina Danalache, Siegmar Reinert, Dorothea Alexander, Andreas Naros
Format: Article
Language:English
Published: Frontiers Media S.A. 2022-10-01
Series:Frontiers in Cell and Developmental Biology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fcell.2022.953516/full
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author Felix Umrath
Felix Umrath
Achim Pfeifer
Wanjing Cen
Marina Danalache
Siegmar Reinert
Dorothea Alexander
Andreas Naros
author_facet Felix Umrath
Felix Umrath
Achim Pfeifer
Wanjing Cen
Marina Danalache
Siegmar Reinert
Dorothea Alexander
Andreas Naros
author_sort Felix Umrath
collection DOAJ
description Dexamethasone (dexa) is commonly used to stimulate osteogenic differentiation of mesenchymal stem/stromal cells (MSCs) in vitro. However, it is paradoxical that glucocorticoids (GCs) such as dexa lead to bone loss and increased fracture risk in patients undergoing glucocorticoid therapy, causing glucocorticoid-induced osteoporosis (GIOP). In a recent publication, we demonstrated that osteogenic differentiation of progenitor cells isolated from jaw periosteal tissue (JPCs) does not depend on dexa, if the medium is supplemented with human platelet lysate (hPL) instead of fetal bovine serum (FBS). This allows the in vitro conditions to be much closer to the natural situation in vivo and enables us to compare osteogenic differentiation with and without dexa. In the present study, we demonstrate that the absence of dexa did not reduce mineralization capacity, but instead slightly improved the osteogenic differentiation of jaw periosteal cells. On the other hand, we show that dexa supplementation strongly alters the gene expression, extracellular matrix (ECM), and cellular communication of jaw periosteal cells. The secretome of periosteal cells previously treated with an osteogenic medium with and without dexa was used to investigate the changes in paracrine secretion caused by dexa. Dexa altered the secretion of several cytokines by jaw periosteal cells and strongly induced osteoclast differentiation of peripheral blood mononuclear cells (PBMCs). This study demonstrates how dexa supplementation can influence the outcome of in vitro studies and highlights a possible role of periosteal cells in the pathogenesis of glucocorticoid-induced osteoporosis. The methods used here can serve as a model for studying bone formation, fracture healing, and various pathological conditions such as (glucocorticoid-induced) osteoporosis, osteoarthritis, bone cancer, and others, in which the interactions of osteoblasts with surrounding cells play a key role.
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spelling doaj.art-897076e259be43989ed37719e9b4ed842022-12-22T04:34:44ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2022-10-011010.3389/fcell.2022.953516953516How osteogenic is dexamethasone?—effect of the corticosteroid on the osteogenesis, extracellular matrix, and secretion of osteoclastogenic factors of jaw periosteum-derived mesenchymal stem/stromal cellsFelix Umrath0Felix Umrath1Achim Pfeifer2Wanjing Cen3Marina Danalache4Siegmar Reinert5Dorothea Alexander6Andreas Naros7Clinic for Oral and Maxillofacial Surgery, University Hospital Tübingen, Tübingen, GermanyClinic for Orthopaedic Surgery, University Hospital Tübingen, Tübingen, GermanyClinic for Oral and Maxillofacial Surgery, University Hospital Tübingen, Tübingen, GermanyClinic for Oral and Maxillofacial Surgery, University Hospital Tübingen, Tübingen, GermanyClinic for Orthopaedic Surgery, University Hospital Tübingen, Tübingen, GermanyClinic for Oral and Maxillofacial Surgery, University Hospital Tübingen, Tübingen, GermanyClinic for Oral and Maxillofacial Surgery, University Hospital Tübingen, Tübingen, GermanyClinic for Oral and Maxillofacial Surgery, University Hospital Tübingen, Tübingen, GermanyDexamethasone (dexa) is commonly used to stimulate osteogenic differentiation of mesenchymal stem/stromal cells (MSCs) in vitro. However, it is paradoxical that glucocorticoids (GCs) such as dexa lead to bone loss and increased fracture risk in patients undergoing glucocorticoid therapy, causing glucocorticoid-induced osteoporosis (GIOP). In a recent publication, we demonstrated that osteogenic differentiation of progenitor cells isolated from jaw periosteal tissue (JPCs) does not depend on dexa, if the medium is supplemented with human platelet lysate (hPL) instead of fetal bovine serum (FBS). This allows the in vitro conditions to be much closer to the natural situation in vivo and enables us to compare osteogenic differentiation with and without dexa. In the present study, we demonstrate that the absence of dexa did not reduce mineralization capacity, but instead slightly improved the osteogenic differentiation of jaw periosteal cells. On the other hand, we show that dexa supplementation strongly alters the gene expression, extracellular matrix (ECM), and cellular communication of jaw periosteal cells. The secretome of periosteal cells previously treated with an osteogenic medium with and without dexa was used to investigate the changes in paracrine secretion caused by dexa. Dexa altered the secretion of several cytokines by jaw periosteal cells and strongly induced osteoclast differentiation of peripheral blood mononuclear cells (PBMCs). This study demonstrates how dexa supplementation can influence the outcome of in vitro studies and highlights a possible role of periosteal cells in the pathogenesis of glucocorticoid-induced osteoporosis. The methods used here can serve as a model for studying bone formation, fracture healing, and various pathological conditions such as (glucocorticoid-induced) osteoporosis, osteoarthritis, bone cancer, and others, in which the interactions of osteoblasts with surrounding cells play a key role.https://www.frontiersin.org/articles/10.3389/fcell.2022.953516/fulldexamethasoneosteogenic differentiationmesenchymal stem/stromal cellsperiosteumosteoclastextracellular matrix
spellingShingle Felix Umrath
Felix Umrath
Achim Pfeifer
Wanjing Cen
Marina Danalache
Siegmar Reinert
Dorothea Alexander
Andreas Naros
How osteogenic is dexamethasone?—effect of the corticosteroid on the osteogenesis, extracellular matrix, and secretion of osteoclastogenic factors of jaw periosteum-derived mesenchymal stem/stromal cells
Frontiers in Cell and Developmental Biology
dexamethasone
osteogenic differentiation
mesenchymal stem/stromal cells
periosteum
osteoclast
extracellular matrix
title How osteogenic is dexamethasone?—effect of the corticosteroid on the osteogenesis, extracellular matrix, and secretion of osteoclastogenic factors of jaw periosteum-derived mesenchymal stem/stromal cells
title_full How osteogenic is dexamethasone?—effect of the corticosteroid on the osteogenesis, extracellular matrix, and secretion of osteoclastogenic factors of jaw periosteum-derived mesenchymal stem/stromal cells
title_fullStr How osteogenic is dexamethasone?—effect of the corticosteroid on the osteogenesis, extracellular matrix, and secretion of osteoclastogenic factors of jaw periosteum-derived mesenchymal stem/stromal cells
title_full_unstemmed How osteogenic is dexamethasone?—effect of the corticosteroid on the osteogenesis, extracellular matrix, and secretion of osteoclastogenic factors of jaw periosteum-derived mesenchymal stem/stromal cells
title_short How osteogenic is dexamethasone?—effect of the corticosteroid on the osteogenesis, extracellular matrix, and secretion of osteoclastogenic factors of jaw periosteum-derived mesenchymal stem/stromal cells
title_sort how osteogenic is dexamethasone effect of the corticosteroid on the osteogenesis extracellular matrix and secretion of osteoclastogenic factors of jaw periosteum derived mesenchymal stem stromal cells
topic dexamethasone
osteogenic differentiation
mesenchymal stem/stromal cells
periosteum
osteoclast
extracellular matrix
url https://www.frontiersin.org/articles/10.3389/fcell.2022.953516/full
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